The requirement of uncoordinated 51-like kinase 1 (ULK1) and ULK2 in the regulation of autophagy
Open accessAbstract
Autophagy is an evolutionarily conserved physiological process of self-digestion by a cell to adapt to various stresses, including starvation. Its molecular basis involves the concerted activation of proteins encoded by the family of autophagy-related (Atg) genes. The best characterized is the serine/threonine protein kinase Atg1 in yeast which appears to be essential at the early stage of autophagy. In mammals, five Atg1 homologues have been identified as uncoordinated (UNC) 51-like kinase 1 to 4 and STK36. ULK1 and ULK2 are the most closely related members of the family, sharing 78% homology within their protein kinase domains. However, the specific function of ULK1 and ULK2 in mammalian autophagy is not fully understood. Here, we demonstrate that ULK1 and ULK2 are functionally redundant protein kinases required to mediate autophagy under nutrient-deprived conditions in fibroblasts. In contrast, ULK1, but not ULK2, is critical to induce the autophagic response of cerebellar granule neurons (CGN) to low potassium concentration in serum-free conditions. Furthermore, we found that ULK1 has a cytoprotective function in neurons. Together, these results provide strong genetic evidence that ULK1 is an essential component of the autophagic signaling pathway. The ability of ULK2 to compensate for the loss of ULK1 function is cell-type specific.
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The ULK2 isoform is a functionally redundant autophagic protein kinase and is ubiquitously expressed such as ULK1.
“recent evidence indicates that the ULK2 isoform is a functionally redundant autophagic protein kinase and is ubiquitously expressed such as ULK1 [45].”
From A gene toolbox for monitoring autophagy transcription (2021) · cites this paper as [45]
The Introduction says ULK1 and ULK2 are ubiquitously expressed protein kinases, and the Discussion finds them functionally redundant for autophagy in primary fibroblasts. The claim omits the paper’s qualification that ULK2’s ability to compensate for ULK1 is cell-type specific; ULK1, but not ULK2, was required for the neuronal response studied. (LLM, conf=0.88)
Experimental — accuracy not yet measuredULK2 can promote autophagy response following starvation.
“As ULK1, ULK2 can promote autophagy response following starvation [45]”
From A gene toolbox for monitoring autophagy transcription (2021) · cites this paper as [45]
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Cites
Autophagy in the Pathogenesis of Disease
Levine, B., & Kroemer, G. (2008) · Cell · doi:10.1016/j.cell.2007.12.018 · Cited by 7,069 · see citing works
LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y., & Yoshimori, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5720 · Cited by 6,605 · see citing works
Ravikumar, B., Vacher, C., Berger, Z., Davies, J. E., Luo, S., Oroz, L. G., Scaravilli, F., Easton, D. F., Duden, R., O'Kane, C. J., et al. (2004) · Nature Genetics · doi:10.1038/ng1362 · Cited by 2,347 · see citing works
Impairment of starvation-induced and constitutive autophagy in <i>Atg7</i> -deficient mice
Komatsu, M., Waguri, S., Ueno, T., Iwata, J., Murata, S., Tanida, I., Ezaki, J., Mizushima, N., Ohsumi, Y., Uchiyama, Y., et al. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200412022 · Cited by 2,331 · see citing works
Nutrient-dependent mTORC1 Association with the ULK1–Atg13–FIP200 Complex Required for Autophagy
Hosokawa, N., Hara, T., Kaizuka, T., Kishi, C., Takamura, A., Miura, Y., Iemura, S.-I., Natsume, T., Takehana, K., Yamada, N., et al. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-12-1248 · Cited by 2,076 · see citing works
Flagged first, then by citations
Research works printed but not linked: 37
- Levine B, Klionsky DJ. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell 2004; 6:463-77.
- Kuma A, Hatano M, Matsui M, Yamamoto A, Nakaya H, Yoshimori T, et al. The role of autophagy during the early neonatal starvation period. Nature 2004; 432:1032-6.
- Ravikumar B, Duden R, Rubinsztein DC. Aggregate- prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy. Hum Mol Genet 2002; 11:1107-17.
- Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, et al. Suppression of basal autophagy in neural cells causes neurodegenera- tive disease in mice. Nature 2006; 441:885-9.
- Komatsu M, Waguri S, Chiba T, Murata S, Iwata J, Tanida I, et al. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 2006; 441:880-4.
- Tsujimoto Y, Shimizu S. Another way to die: auto- phagic programmed cell death. Cell Death Differ 2005; 12:1528-34.
- Tsukada M, Ohsumi Y. Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevi- siae. FEBS Lett 1993; 333:169-74.
- Suzuki K, Ohsumi Y. Molecular machinery of auto- phagosome formation in yeast, Saccharomyces cerevisiae. FEBS Lett 2007; 581:2156-61.
- Kabeya Y, Kamada Y, Baba M, Takikawa H, Sasaki M, Ohsumi Y. Atg17 functions in cooperation with Atg1 and Atg13 in yeast autophagy. Mol Biol Cell 2005; 16:2544-53.
- Kamada Y, Funakoshi T, Shintani T, Nagano K, Ohsumi M, Ohsumi Y. Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J Cell Biol 2000; 150:1507-13.
- Jung CH, Jun CB, Ro SH, Kim YM, Otto NM, Cao J, et al. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell 2009; 20:1992-2003.
- Ganley IG, Lam du H, Wang J, Ding X, Chen S, Jiang X. ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy. J Biol Chem 2009; 284:12297-305.
- Hara T, Takamura A, Kishi C, Iemura S, Natsume T, Guan JL, et al. FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells. J Cell Biol 2008; 181:497-510.
- Chan EY, Longatti A, McKnight NC, Tooze SA. Kinase-inactivated ULK proteins inhibit autophagy via their conserved C-terminal domains using an Atg13-independent mechanism. Mol Cell Biol 2009; 29:157-71.
- Kundu M, Lindsten T, Yang CY, Wu J, Zhao F, Zhang J, et al. Ulk1 plays a critical role in the autophagic clearance of mitochondria and ribosomes during reticu- locyte maturation. Blood 2008; 112:1493-502.
- Chan EY, Kir S, Tooze SA. siRNA screening of the kinome identifies ULK1 as a multidomain modulator of autophagy. J Biol Chem 2007; 282:25464-74.
- Young AR, Chan EY, Hu XW, Köchl R, Crawshaw SG, High S, et al. Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes. J Cell Sci 2006; 119:3888-900.
- Bjørkøy G, Lamark T, Brech A, Outzen H, Perander M, Overvatn A, et al. p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol 2005; 171:603-14.
- Mizushima N, Yamamoto A, Matsui M, Yoshimori T, Ohsumi Y. In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell 2004; 15:1101-11.
- Contestabile A. Cerebellar granule cells as a model to study mechanisms of neuronal apoptosis or survival in vivo and in vitro. Cerebellum 2002; 1:41-55.
- Canu N, Tufi R, Serafino AL, Amadoro G, Ciotti MT, Calissano P. Role of the autophagic-lysosomal system on low potassium-induced apoptosis in cultured cer- ebellar granule cells. J Neurochem 2005; 92:1228-42.
- Boya P, González-Polo RA, Casares N, Perfettini JL, Dessen P, Larochette N, et al. Inhibition of macro- autophagy triggers apoptosis. Mol Cell Biol 2005; 25:1025-40.
- Rich T, Watson CJ, Wyllie A. Apoptosis: the germs of death. Nat Cell Biol 1999; 1:69-71.
- Pyo JO, Jang MH, Kwon YK, Lee HJ, Jun JI, Woo HN, et al. Essential roles of Atg5 and FADD in auto- phagic cell death: dissection of autophagic cell death into vacuole formation and cell death. J Biol Chem 2005; 280:20722-9.
- Joza N, Susin SA, Daugas E, Stanford WL, Cho SK, Li CY, et al. Essential role of the mitochondrial apoptosis- inducing factor in programmed cell death. Nature 2001; 410:549-54.
- Slagsvold HH, Rosseland CM, Jacobs C, Khuong E, Kristoffersen N, Gaarder M, et al. High molecular weight DNA fragments are processed by caspase sensi- tive or caspase independent pathways in cultures of cer- ebellar granule neurons. Brain Res 2003; 984:111-21.
- Maycotte P, Guemez-Gamboa A, Moran J. Apoptosis and autophagy in rat cerebellar granule neuron death: Role of reactive oxygen species. J Neurosci Res 2010; 88:73-85.
- Zhou X, Babu JR, da Silva S, Shu Q, Graef IA, Oliver T, et al. Unc-51-like kinase 1/2-mediated endocytic processes regulate filopodia extension and branch- ing of sensory axons. Proc Natl Acad Sci USA 2007; 104:5842-7.
- Tomoda T, Bhatt RS, Kuroyanagi H, Shirasawa T, Hatten MEA. Mouse serine/threonine kinase homolo- gous to C. elegans UNC51 functions in parallel fiber formation of cerebellar granule neurons. Neuron 1999; 24:833-46.
- Chan EY, Longatti A, McKnight NC, Tooze SA. Kinase-inactivated ULK proteins inhibit autophagy via their conserved C-terminal domains using an Atg13-independent mechanism. Mol Cell Biol 2009; 29:157-71.
- Chan EY, Tooze SA. Evolution of Atg1 function and regulation. Autophagy 2009; 5:758-65.
- Scott RC, Schuldiner O, Neufeld TP. Role and regula- tion of starvation-induced autophagy in the Drosophila fat body. Dev Cell 2004; 7:167-78.
- Noda T, Ohsumi Y. Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J Biol Chem 1998; 273:3963-6.
- Young JE, Martinez RA, La Spada AR. Nutrient deprivation induces neuronal autophagy and implicates reduced insulin signaling in neuroprotective autophagy activation. J Biol Chem 2009; 284:2363-73.
- Tournier C, Hess P, Yang DD, Xu J, Turner TK, Nimnual A, et al. Requirement of JNK for stress- induced activation of the cytochrome c-mediated death pathway. Science 2000; 288:870-4.
- Courtney MJ, Nicholls DG. Interactions between phos- pholipase C-coupled and NMDA receptor in cultured cerebellar granule cells: protein kinase C-mediated inhibition of NMDA responses. J Neurochem 1992; 59:983-92.
- Kayahara M, Wang X, Tournier C. Selective regula- tion of c-jun gene expression by the mitogen-activated protein kinases via the TPA-responsive element and the myocyte enhancer factor 2 binding sites. Mol Cell Biol 2005; 25:3784-92.
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Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,622 · see citing works
Self-citationULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase
Russell, R. C., Tian, Y., Yuan, H., Park, H. W., Chang, Y.-Y., Kim, J., Kim, H., Neufeld, T. P., Dillin, A. G., & Guan, K. (2013) · Nature Cell Biology · doi:10.1038/ncb2757 · Cited by 1,586 · see citing works
“The Beclin-1 S-T(4,7,10,14,29,42) A mutant was not phosphorylated by ULK1 (Fig.”
BackgroundMethodInfluentialRole of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks
Alers, S., Löffler, A. S., Wesselborg, S., & Stork, B. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.06159-11 · Cited by 1,483 · see citing works
“However, in contrast to the knockout of other essential autophagy-related genes (56, 59), ulk1 / and ulk2 / mice are born viable and are able to survive the short starvation period after birth (13, 60, 62).”
BackgroundThe mammalian ULK1 complex and autophagy initiation
Zachari, M., & Ganley, I. G. (2017) · Essays in Biochemistry · doi:10.1042/ebc20170021 · Cited by 789 · see citing works
Autophagy-Dependent Ferroptosis: Machinery and Regulation
Liu, J., Kuang, F.-M., Kroemer, G., Klionsky, D., Kang, R., & Tang, D. (2020) · Cell Chemical Biology · doi:10.1016/j.chembiol.2020.02.005 · Cited by 763 · see citing works
“ULK1 and ULK2 may have some functional redundancy in autophagy induction, although they share only 52% amino acid identity (Lee and Tournier, 2011).”
BackgroundAutophagy regulation by nutrient signaling
Russell, R. C., Yuan, H., & Guan, K. (2013) · Cell Research · doi:10.1038/cr.2013.166 · Cited by 713 · see citing works
Huntingtin functions as a scaffold for selective macroautophagy
Rui, Y.-N., Xu, Z., Patel, B., Chen, Z., Chen, D., Tito, A., David, G., Sun, Y., Stimming, E. F., Bellen, H. J., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3101 · Cited by 423 · see citing works
Unique role for ATG5 in neutrophil-mediated immunopathology during M. tuberculosis infection
Kimmey, J. M., Huynh, J. P., Weiss, L. A., Park, S., Kambal, A., Debnath, J., Virgin, H. W., & Stallings, C. L. (2015) · Nature · doi:10.1038/nature16451 · Cited by 382 · see citing works
Wong, P., Puente, C., Ganley, I. G., & Jiang, X. (2013) · Autophagy · doi:10.4161/auto.23323 · Cited by 494 · see citing works
Machine learning identifies candidates for drug repurposing in Alzheimer’s disease
Rodriguez, S., Hug, C., Todorov, P., Moret, N., Boswell, S. A., Evans, K., Zhou, G., Johnson, N. T., Hyman, B. T., Sorger, P. K., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21330-0 · Cited by 299 · see citing works
Autophagosome formation—The role of ULK1 and Beclin1–PI3KC3 complexes in setting the stage
Wirth, M., Joachim, J., & Tooze, S. A. (2013) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2013.05.007 · Cited by 277 · see citing works
Wang, J., Zhu, P., Li, R., Ren, J. T., & Zhou, H. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101415 · Cited by 221 · see citing works
“In fact, autophagyrelated compensatory mechanism was first described in Ulk1-knockout mice [49,50].”
BackgroundMartin, K. R., Celano, S. L., Solitro, A. R., Günaydin, H., Scott, M., O’Hagan, R. C., Shumway, S. D., Fuller, P. H., & MacKeigan, J. P. (2018) · iScience · doi:10.1016/j.isci.2018.09.012 · Cited by 191 · see citing works
Li, Z., Li, J., & Tang, N. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.04.017 · Cited by 172 · see citing works
Regulation of nutrient-sensitive autophagy by uncoordinated 51-like kinases 1 and 2
McAlpine, F. E., Williamson, L. E., Tooze, S. A., & Chan, E. Y. W. (2013) · Autophagy · doi:10.4161/auto.23066 · Cited by 150 · see citing works
“Ulk2-null mice are also born without phenotype and the corresponding MEFs show normal autophagy.(26) However, Ulk1 knockout mice do display defects in mitochondrial autophagy during erythrocyte development and in primary hepatocytes.”
BackgroundMethodInfluentialTargeting Autophagy for Cancer Treatment and Tumor Chemosensitization
Pérez-Hernández, M., Arias, A., Martínez‐García, D., Pérez‐Tomás, R., Quesada, R., & Soto‐Cerrato, V. (2019) · Cancers · doi:10.3390/cancers11101599 · Cited by 152 · see citing works
“The role of ULK1 is essential for the initiation of autophagy [15,160,161], however the role of ULK2 in autophagy seems to be cell type dependent [162].”
BackgroundAtg13 and FIP200 act independently of Ulk1 and Ulk2 in autophagy induction
Alers, S., Löffler, A. S., Paasch, F., Dieterle, A. M., Keppeler, H., Lauber, K., Campbell, D. G., Fehrenbacher, B., Schaller, M., Wesselborg, S., et al. (2011) · Autophagy · doi:10.4161/auto.7.12.18027 · Cited by 138 · see citing works
A gene toolbox for monitoring autophagy transcription
Bordi, M., De Cegli, R., Testa, B., Nixon, R. A., Ballabio, A., & Cecconi, F. (2021) · Cell Death & Disease · doi:10.1038/s41419-021-04121-9 · Cited by 131 · see citing works
“Within each category, we classified genes in groups based on their functions along the pathway (i.e., ATG8 Ubiquitinlike conjugation systems) or, in other cases, based on their subcellular localization (i.e., lysosome) or, lastly, based on the composition of specific complexes (such as MTOR complex 1 or ULK1 complex)…”
BackgroundInfluentialWu, L., Feng, Z., Cui, S., Hou, K., Tang, L., Zhou, J., Cai, G., Xie, Y., Hong, Q., Fu, B., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0063799 · Cited by 117 · see citing works
“Recent studies have found that mTOR inhibits autophagy by producing ULK1, a member of the autophagy initiation associated complex ULK1-ATG13-FIP200, resulting in loss of its kinase activity by phosphorylating Ser757, and participating in a variety of pathological and physiological processes [13,14,15,16,17,18,19,20].”
BackgroundJamart, C., Benoit, N., Raymackers, J.-M., Kim, H. J., Kim, C. K., & Francaux, M. (2012) · European Journal of Applied Physiology · doi:10.1007/s00421-011-2287-3 · Cited by 121 · see citing works
So Many Roads: the Multifaceted Regulation of Autophagy Induction
Velazquez, A. C., & Jackson, W. T. (2018) · Molecular and Cellular Biology · doi:10.1128/mcb.00303-18 · Cited by 130 · see citing works
“Of these kinases, ULK1 and ULK2 have been characterized as autophagy-specific regulators with at least partially overlapping autophagy functions (1, 20).”
BackgroundDong, Y., Zhang, X., Xie, M., Arefnezhad, B., Wang, Z., Wang, W., Feng, S., Huang, G., Guan, R., Shen, W., et al. (2015) · BMC Genomics · doi:10.1186/s12864-015-1606-1 · Cited by 116 · see citing works
Kruppel-like factor 4 is critical for transcriptional control of cardiac mitochondrial homeostasis
Liao, X., Zhang, R., Lu, Y., Prosdocimo, D. A., Sangwung, P., Zhang, L., Zhou, G., Anand, P., Lai, L., Leone, T. C., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci79964 · Cited by 139 · see citing works
Distinct functions ofUlk1andUlk2in the regulation of lipid metabolism in adipocytes
Ro, S., Jung, C. H., Hahn, W. S., Xu, X. M., Kim, Y. M., Yun, Y. S., Park, J.-M., Kim, K., Seo, M., Ha, T. Y., et al. (2013) · Autophagy · doi:10.4161/auto.26563 · Cited by 92 · see citing works
Non-apoptotic cell death in malignant tumor cells and natural compounds
Ye, J., Zhang, R., Wu, F., Zhai, L., Wang, K., Xiao, M., Xie, T., & Sui, X. (2018) · Cancer Letters · doi:10.1016/j.canlet.2018.01.061 · Cited by 102 · see citing works
The Importance of Autophagy Regulation in Breast Cancer Development and Treatment
Zarzynska, J. M. (2014) · BioMed Research International · doi:10.1155/2014/710345 · Cited by 82 · see citing works
“AdipoQ is potentially able to regulate autophagy through AMPK, whose activation has been observed in breast cancer cells [55, 56].”
BackgroundAlers, S., Löffler, A. S., Wesselborg, S., & Stork, B. (2012) · Cell Communication and Signaling · doi:10.1186/1478-811x-10-7 · Cited by 89 · see citing works
“The single knockdown of individual components, however, has remarkably differing effects on autophagy initiation [53-56,63,68,75,76,85].”
BackgroundMembrane Trafficking in Autophagy
Søreng, K., Neufeld, T. P., & Simonsen, A. (2017) · International review of cytology · doi:10.1016/bs.ircmb.2017.07.001 · Cited by 110 · see citing works
Shukla, S. K., Patric, I. R. P., Patil, V. S., Shwetha, S. D., Hegde, A. S., Chandramouli, B. A., Arivazhagan, A., Santosh, V., & Somasundaram, K. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.567032 · Cited by 92 · see citing works
“ULK2 is one of the two mammalian homologues of UNC-51 of Caenorhabditis elegans and APG/Atg1 of Saccharomyces cerevisiae and is the upstream initiator of autophagy (38).”
BackgroundPhospho-ΔNp63α/miR-885-3p axis in tumor cell life and cell death upon cisplatin exposure
Huang, Y.-P., Chuang, A., & Ratovitski, E. (2011) · Cell Cycle · doi:10.4161/cc.10.22.18107 · Cited by 87 · see citing works
Differential and convergent utilization of autophagy components by positive-strand RNA viruses
Abernathy, E., Mateo, R., Majzoub, K., van Buuren, N. J., Bird, S. W., Carette, J. E., & Kirkegaard, K. (2019) · PLoS Biology · doi:10.1371/journal.pbio.2006926 · Cited by 82 · see citing works
“We additionally tested whether a double knock down of ULK1 and ULK2 affected DENV growth, given that ULK1 and ULK2 can be redundant in some cell types [9, 52] .”
BackgroundCentral Role of ULK1 in Type I Interferon Signaling
Saleiro, D., Mehrotra, S., Kroczynska, B., Beauchamp, E. M., Lisowski, P., Majchrzak-Kita, B., Bhagat, T., Stein, B., McMahon, B., Altman, J., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.03.056 · Cited by 68 · see citing works
“, 2011), as ULK1 and ULK2 kinases were previously shown to have at least partially redundant functions in fibroblasts (Kundu et al., 2008; Lee and Tournier, 2011).”
BackgroundMethodRegulation and Function of Uncoordinated-51 Like Kinase Proteins
Chan, E. Y. W. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4396 · Cited by 65 · see citing works
“The idea of ULK1/2 redundancy is further supported by the lack of strong phenotype after ULK2 knockout (5, 27).”
Mito-protective autophagy is impaired in erythroid cells of aged mtDNA-mutator mice.
Li-Harms, X., Milasta, S., Lynch, J., Wright, C., Joshi, A., Iyengar, R., Neale, G., Wang, X., Wang, Y.-D., Prolla, T., et al. (2015) · Blood · doi:10.1182/blood-2014-07-586396 · Cited by 67 · see citing works
GSK3B induces autophagy by phosphorylating ULK1
Ryu, H. Y., Kim, L. E., Jeong, H., Yeo, B. K., Lee, J., Nam, H., Ha, S., An, H., Park, H., Jung, S., et al. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00570-6 · Cited by 78 · see citing works
Autophagy, Cell Viability and Chemo-resistance are Regulated by miR-489 in Breast Cancer
Soni, M., Patel, Y., Markoutsa, E., Jie, C.-F., Liu, S., Xu, P.-S., & Chen, H.-X. (2018) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-17-0634 · Cited by 63 · see citing works
“Studies show that ULK1 and ULK2 (homolog of ULK1) possess redundant roles in autophagy (42, 43) and indeed, it takes a double knockout of Ulk1 and Ulk2 to completely block amino acid starvation-induced autophagy in mouse embryonic fibroblasts (44).”
BackgroundTumor-derived extracellular vesicles in breast cancer: From bench to bedside
Wang, H., & Gires, O. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.06.012 · Cited by 67 · see citing works
Lieberman, O. J., & Sulzer, D. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.12.028 · Cited by 65 · see citing works
“ULK2, a ULK1 homolog in mammalian cells, may also control autophagy but it is presently unclear whether these kinases are redundant [24,28].”
BackgroundAn antibody for analysis of autophagy induction
Tian, W., Alsaadi, R. M., Guo, Z., Kalinina, A., Carrier, M., Tremblay, M., Lacoste, B., Lagace, D. C., & Russell, R. C. (2019) · Nature Methods · doi:10.1038/s41592-019-0661-y · Cited by 75 · see citing works
Saleiro, D., & Platanias, L. C. (2019) · Seminars in Immunology · doi:10.1016/j.smim.2019.101299 · Cited by 72 · see citing works
Antimicrobial Autophagy: A Conserved Innate Immune Response in Drosophila
Moy, R. H., & Cherry, S. R. (2013) · Journal of Innate Immunity · doi:10.1159/000350326 · Cited by 3,549 · see citing works
Novel Insight Into the Development and Function of Hypopharyngeal Glands in Honey Bees
Ahmad, S., Khan, S. A., Khan, K. A., & Li, J.-K. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2020.615830 · Cited by 56 · see citing works
McCrary, M. R., Jiang, M., Giddens, M. M., Zhang, J., Owino, S., Wei, Z. Z., Zhong, W., Gu, X.-H., Xin, H., Hall, R., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201900070r · Cited by 54 · see citing works
“LC3-II is implicated in autophagosome fusion with lysosomes during macroautophagy (43).”
BackgroundInfluentialChen, J., Shen, B., & Jiang, Z. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.978558 · Cited by 52 · see citing works
Kannangara, A. R., Poole, D. M., McEwan, C. M., Youngs, J. C., Weeresekara, V., Thornock, A. M., Lazaro, M. T., Balasooriya, E. R., Oh, L. M., Soderblom, E. J., et al. (2021) · EMBO Reports · doi:10.15252/embr.202051136 · Cited by 63 · see citing works
“Mice lacking ULK1, and its semi-redundant homologue ULK2, succumb to a neonatal lethality during the weening period, similar to the loss of other core autophagy genes (Chan et al , 2007; Kundu et al , 2008; Cheong et al , 2011; Lee & Tournier, 2011).”
Systematic analysis of ATG13 domain requirements for autophagy induction
Hieke, N., Verma, N., Schlütermann, D., Berleth, N., Deitersen, J., Böhler, P., Stuhldreier, F., Wu, W., Seggewiß, S., Peter, C., et al. (2017) · Autophagy · doi:10.1080/15548627.2017.1387342 · Cited by 59 · see citing works
Poliovirus induces autophagic signaling independent of the ULK1 complex
Velazquez, A. C., Corona, A. K., Klein, K. A., & Jackson, W. (2018) · Autophagy · doi:10.1080/15548627.2018.1458805 · Cited by 49 · see citing works
“Evidence suggests that the ULK1-containing complex sends the primary signal for autophagic activation, with ULK2 playing a minor role [18,19].”
BackgroundSotthibundhu, A., Promjuntuek, W., Liu, M., Shen, S., & Noisa, P. (2018) · Cell and Tissue Research · doi:10.1007/s00441-018-2829-7 · Cited by 57 · see citing works
Neuroinflammation and Autophagy in Parkinson’s Disease—Novel Perspectives
Minchev, D. S., Kazakova, M., & Sarafian, V. S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232314997 · Cited by 53 · see citing works
Physiological functions of ULK1/2
Pareek, G., & Kundu, M. (2024) · Journal of Molecular Biology · doi:10.1016/j.jmb.2024.168472 · Cited by 49 · see citing works
Conservation of structure, function and inhibitor binding in UNC-51-like kinase 1 and 2 (ULK1/2)
Chaikuad, A., Koschade, S. E., Stolz, A., Živković, K., Pohl, C., Shaid, S., Ren, H., Lambert, L. J., Cosford, N., Brandts, C., et al. (2019) · bioRxiv · doi:10.1101/550111 · Cited by 46
Miki, Y., Tanji, K., Mori, F., Utsumi, J., Sasaki, H., Kakita, A., Takahashi, H., & Wakabayashi, K. (2016) · Brain Pathology · doi:10.1111/bpa.12297 · Cited by 46 · see citing works
“Upon inhibition of mTOR, ULK1 is activated and triggers the phosphorylation of ATG13 and FIP200, thus initiating autophagy (19).”
BackgroundDemeter, A., Romero-Mulero, M. C., Csabai, L., Olbei, M. L., Sudhakar, P., Haerty, W., & Korcsmaros, T. D. (2020) · Scientific Reports · doi:10.1038/s41598-020-67780-2 · Cited by 49 · see citing works
miR-338 modulates proliferation and autophagy by PI3K/AKT/mTOR signaling pathway in cervical cancer.
Lu, R., Yang, Z., Xu, G., & Yu, S.-Y. (2018) · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · doi:10.1016/j.biopha.2018.06.024 · Cited by 45 · see citing works
Sun, Y., Li, T. Y., Song, L., Zhang, C., Li, J., Lin, Z., Lin, S., & Lin, S. (2018) · Hepatology · doi:10.1002/hep.29759 · Cited by 43 · see citing works
“Ulk1 mice((29)) and Ulk2 mice((30)) were obtained from Jackson Laboratory, ME, USA (B6.”
BackgroundMethodTranscriptional Repressor DAXX Promotes Prostate Cancer Tumorigenicity via Suppression of Autophagy*
Puto, L. A., Brognard, J., & Hunter, T. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.658765 · Cited by 42 · see citing works
“Because ULK1 and its closely related family member ULK2 may have redundant functions, and, in some cells, one may compensate for the lack of the other (21), we checked the ULK2 protein levels in PC3 cells.”
BackgroundGong, J., Gu, H., Zhao, L., Wang, L., Liu, P., Wang, F., Xu, H., & Zhao, T. (2018) · Cell Death and Disease · doi:10.1038/s41419-017-0054-z · Cited by 45 · see citing works
Liu, X., Hu, X., Kuang, Y., Yan, P., Li, L., Li, C., Tao, Q., & Cai, X. (2017) · Cancer Letters · doi:10.1016/j.canlet.2017.02.030 · Cited by 45 · see citing works
“In our study, ULK1 consistently increased, while p-ULK1(Ser757) decreased significantly in BCLB-transfected cells, especially after starvation.”
BackgroundInfluentialde Almeida, D. C., Bassi, Ê. J., de Azevedo, H. F. Z., Anderson, L., Origassa, C. S. T., Cenedeze, M. A., Andrade‐Oliveira, V., Felizardo, R. J. F., Silva, R. C., Hiyane, M. I., et al. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00645 · Cited by 42 · see citing works
Ulk4 Is Essential for Ciliogenesis and CSF Flow
Liu, M., Guan, Z., Shen, Q., Lalor, P., FitzGerald, U., O’Brien, T., Dockery, P., & Shen, S. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.0621-16.2016 · Cited by 50 · see citing works
“Ulk1 and Ulk2 are major regulators of autophagy (Egan et al., 2011; Lee and Tournier, 2011), whereas Ulk3 is involved in Shh signaling (Fuccillo et al., 2006).”
BackgroundSignaling by Type I Interferons in Immune Cells: Disease Consequences
Ζαννίκου, Μ., Fish, E. N., & Platanias, L. C. (2024) · Cancers · doi:10.3390/cancers16081600 · Cited by 40 · see citing works
“ULK1, the mammalian homolog of the UNC-51 kinase of Caenorhabditis elegans , is necessary for activating p38 MAPK and the transcription of ISGs involved in anti-cancer effects and responses [52–54].”
BackgroundCombination of ULK1 and LC3B improve prognosis assessment of hepatocellular carcinoma.
Wu, D.-H., Wang, T.-T., Ruan, D., Li, X., Chen, Z.-H., Wen, J.-Y., Lin, Q., Ma, X.-K., Wu, X.-Y., & Jia, C.-C. (2017) · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · doi:10.1016/j.biopha.2017.10.025 · Cited by 39
Liu, E., Corcino, Y. L., Portillo, J. C., Miao, Y., & Subauste, C. S. (2016) · Infection and Immunity · doi:10.1128/iai.00101-16 · Cited by 37 · see citing works
“However, similarly to our studies, a deficiency of ULK1 was sufficient to impair autophagy in human embryonal kidney 293 cells subjected to amino acid starvation or treated with rapamycin and in cerebellar granule neurons exposed to low-potassium and serum-free conditions (42, 43).”
BackgroundResultVucicevic, L. M., Misirkic-Marjanovic, M., Ćirić, D., Martinović, T., Jovanović, M., Isaković, A., Marković, I., Šaponjić, J., Foretz, M., Rabanal‐Ruiz, Y., et al. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03356-2 · Cited by 37 · see citing works
Kim, Y. H., Baek, S. H., Kim, E. K., Ha, J. M., Jin, S. Y., Lee, H. S., Ha, H. K., Song, S. H., Kim, S. J., Shin, H. K., et al. (2016) · FEBS Letters · doi:10.1002/1873-3468.12172 · Cited by 40 · see citing works
Enhancing Anti-Cancer Therapy with Selective Autophagy Inhibitors by Targeting Protective Autophagy
Lee, M. J., Park, J., Jo, S. B., & Joe, Y. A. (2022) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2022.153 · Cited by 44 · see citing works
“…show no obvious defective phenotypes with close-to-normal development partly due to functional redundancy (Cann et al., 2008; Kundu et al., 2008; Marino et al., 2010; Lee and Tournier, 2011; Groza et al., 2022) (International Mouse Phenotyping Consortium [IMPC], https://www.mousephenotype.org/).”
BackgroundFuqua, J. D., Mere, C., Kronemberger, A., Blomme, J., Bae, D., Turner, K., Harris, M. P., Scudese, E., Edwards, M., Ebert, S. M., et al. (2019) · The FASEB Journal · doi:10.1096/fj.201900766r · Cited by 48 · see citing works
Xue, H., Ji, Y., Wei, S., Yu, Y., Yan, X., Liu, S., Zhang, M., Fan, Y., Lan, X., & Chen, L. (2016) · Life Sciences · doi:10.1016/j.lfs.2016.04.004 · Cited by 33 · see citing works
Chen, Y., Wang, S., Zhang, L., Xie, T., Song, S., Huang, J., Zhang, Y., Ouyang, L., & Liu, B. (2015) · Scientific Reports · doi:10.1038/srep11035 · Cited by 34 · see citing works
Qi, Y., Fan, P., Hao, Y., Han, B., Fang, Y., Mao, F., Cui, Z., & Li, J. (2015) · Journal of Proteome Research · doi:10.1021/acs.jproteome.5b00530 · Cited by 38 · see citing works
Alers, S., Wesselborg, S., & Stork, B. (2014) · Autophagy · doi:10.4161/auto.28987 · Cited by 62 · see citing works
Brucella mediates autophagy, inflammation, and apoptosis to escape host killing
Qin, Y.-Q., Zhou, G., Jiao, F., Cheng, C., Meng, C., Wang, L., Wu, S., Fan, C.-L., Li, J., Zhou, B., et al. (2024) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2024.1408407 · Cited by 31
Identification of eQTLs and sQTLs associated with meat quality in beef
Leal-Gutiérrez, J. D., Elzo, M., & Mateescu, R. (2019) · BMC Genomics · doi:10.1186/s12864-020-6520-5 · Cited by 28 · see citing works
Control of cortex development by ULK4, a rare risk gene for mental disorders including schizophrenia
Lang, B., Zhang, L., Jiang, G., Hu, L., Lan, W., Zhao, L., Hunter, I., Pruski, M., Song, N., Huang, Y., et al. (2016) · Scientific Reports · doi:10.1038/srep31126 · Cited by 35 · see citing works
PKCλ/ι inhibition activates an ULK2-mediated interferon response to repress tumorigenesis
Linares, J. F., Zhang, X., Martínez-Ordóñez, A., Durán, Á., Kinoshita, H., Kasashima, H., Nakanishi, N., Nakanishi, Y., Carelli, R., Cappelli, L. V., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.08.039 · Cited by 27 · see citing works
Identification of the autophagy pathway in a mollusk bivalve, Crassostrea gigas
Picot, S., Faury, N., Arzul, I., Chollet, B., Renault, T., & Morga, B. (2020) · Autophagy · doi:10.1080/15548627.2020.1713643 · Cited by 27 · see citing works
Kurdi, A., Doncker, M. D., Leloup, A. J. A., Neels, H. M., Timmermans, J., Lemmens, K., Apers, S., Meyer, G. R. Y. D., & Martinet, W. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13626 · Cited by 25 · see citing works
Linking adiponectin and autophagy in the regulation of breast cancer metastasis
Libby, E. F., Frost, A. R., Demark‐Wahnefried, W., & Hurst, D. R. (2014) · Journal of Molecular Medicine · doi:10.1007/s00109-014-1179-5 · Cited by 27 · see citing works
Role of lncRNAs in the Development of Ischemic Stroke and Their Therapeutic Potential
Vasudeva, K., Dutta, A., & Munshi, A. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02359-0 · Cited by 26 · see citing works
The STING controlled cytosolic-DNA activated innate immune pathway and microbial disease
Konno, H., & Barber, G. N. (2014) · Microbes and Infection · doi:10.1016/j.micinf.2014.10.002 · Cited by 25 · see citing works
Perinatal versus adult loss of ULK1 and ULK2 distinctly influences cardiac autophagy and function
Harris, M. P., Zhang, Q. J., Cochran, C. T., Ponce, J., Alexander, S., Kronemberger, A., Fuqua, J. D., Zhang, Y., Fattal, R., Harper, T., et al. (2022) · Autophagy · doi:10.1080/15548627.2021.2022289 · Cited by 23 · see citing works
Kumar, M., & Papaleo, E. (2020) · Scientific Reports · doi:10.1038/s41598-020-71527-4 · Cited by 26 · see citing works
Hu, M., Chen, N., Chen, M., Chen, F., Lu, Y., Xu, Y., Yang, L., Zeng, H., Shen, M., Chen, X., et al. (2023) · Leukemia · doi:10.1038/s41375-023-01907-y · Cited by 27 · see citing works
“ULK1/ULK2 was originally defined as a core component of the autophagy initiation complex [52].”
BackgroundThe Secrets of Alternative Autophagy
Urbańska, K., & Orzechowski, A. (2021) · Cells · doi:10.3390/cells10113241 · Cited by 28 · see citing works
“These events suppress ULK1 catalytic activity, which results in autophagy inhibition.”
BackgroundInfluentialLncRNA MALAT1 and Ischemic Stroke: Pathogenesis and Opportunities
Khoshnam, S., Moalemnia, A., Anbiyaee, O., Farzaneh, M., & Ghaderi, S. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03853-3 · Cited by 23
Nichenko, A. S., Sorensen, J. R., Southern, W. M., Qualls, A., Schifino, A. G., McFaline‐Figueroa, J., Blum, J., Tehrani, K. F., Yin, H., Mortensen, L. J., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041937 · Cited by 26 · see citing works
“Toward that end, it has been suggested that the Ulk2, a homologue of Ulk1 that shares 78% of its protein kinase domain, may be upregulated to compensate for the loss of Ulk1 [47].”
BackgroundUnravelling the multifaceted roles of Atg proteins to improve cancer therapy
Chen, Y., Liu, X. ‐., Yin, Y., Lee, C. ‐., Wang, F., Liu, H., Wu, X., & Liu, J. (2014) · Cell Proliferation · doi:10.1111/cpr.12095 · Cited by 25 · see citing works
Targeting Autophagy Using Saponins as a Therapeutic and Preventive Strategy against Human Diseases.
Han, B., & He, C.-W. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105428 · Cited by 22 · see citing works
Li, Z., Zhao, K., Lv, X., Lan, Y., Hu, S., Shi, J., Guan, J., Yang, Y., Lu, H., He, H., et al. (2018) · Journal of Virology · doi:10.1128/jvi.00325-18 · Cited by 25 · see citing works
“Ulk1 and Ulk2 die within 24 h of birth, implying that these two kinases appear to compensate for the loss of each other (33, 34).”
BackgroundULK3-dependent activation of GLI1 promotes DNMT3A expression upon autophagy induction
González-Rodríguez, P., Cheray, M., Keane, L., Engskog‐Vlachos, P., & Joseph, B. (2022) · Autophagy · doi:10.1080/15548627.2022.2039993 · Cited by 21 · see citing works
“Whereas a role for ULK1 and ULK2, mammalian homolog of the yeast Atg1, and somehow redundant kinases, in the regulation of autophagy is well established [38], the function of ULK3 in this process remains unclear.”
BackgroundmiR‐26a suppresses autophagy in swine Sertoli cells by targeting ULK2
Ran, M.-L., Li, Z., Cao, R., Weng, B., Peng, F.-Z., He, C., & Chen, B. (2018) · Reproduction in domestic animals = Zuchthygiene · doi:10.1111/rda.13177 · Cited by 21 · see citing works
Autophagy-independent function of Atg1 for apoptosis-induced compensatory proliferation
Li, M., Lindblad, J. L., Perez, E., Bergmann, A., & Fan, Y. (2016) · BMC Biology · doi:10.1186/s12915-016-0293-y · Cited by 25 · see citing works
“This function of ULK proteins is conserved in evolution [6–9].”
BackgroundHashemi, M., Khosroshahi, E. M., Tanha, M., Khoushab, S., Bizhanpour, A., Azizi, F., Mohammadzadeh, M., Matinahmadi, A., Koohpar, Z. K., Asadi, S., et al. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e37376 · Cited by 23 · see citing works
“In tumor models with mutated LKB1, the production of immune peptides is inhibited; the suppression of Unc-51-like kinase 1 (ULK1), as an autophagy modulator, can reverse these conditions by enhancing the immu-noproteasome expression [235].”
BackgroundMicroRNA machinery in Parkinson’s disease: a platform for neurodegenerative diseases
Saghazadeh, A., & Rezaei, N. (2015) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2015.1114886 · Cited by 19 · see citing works
“ULK1 exerts a neuroprotective effect with eliciting the autophagy response.[54] In SHSY5Y cells, it has been shown that miR-595 induces the ULK1 expression and corresponding autophagy response, whereas miR-4487 plays an inhibitory role in stimulating this process.”
BackgroundZhou, C.-T., Li, A., Liu, S., & Sun, H. (2021) · Biology · doi:10.3390/biology10050375 · Cited by 18
“ULK2 is a serine/threonine kinase that participates in autophagosome formation and initiation of autophagy [64].”
BackgroundNing, X.-H., & Sun, L. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124252 · Cited by 18 · see citing works
Li, Z., Lan, Y., Zhao, K., Lv, X., Ding, N., Lu, H., Zhang, J., Huiqing, Y., Shi, J., Song, D., et al. (2017) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2017.00155 · Cited by 18 · see citing works
“Earlier research showed that Ulk1 is required for endocytosis in response to NGF/TrkA complexes (Pelkmans et al., 2005; Zhou et al., 2007; Lee and Tournier, 2011), and PHEV used the endo-/exocytosis for transsynaptic transfer (Li et al., 2013).”
MethodBeyond autophagy: New roles for ULK1 in immune signaling and interferon responses
Saleiro, D., Kościuczuk, E. M., & Platanias, L. C. (2016) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2016.03.008 · Cited by 22 · see citing works
“Additionally, ULK1 directly phosphorylates Syntenin-1 impeding its binding to ubiquitin [65] and plays a cytoprotective role in neurons [2].”
InfluentialReduced ULK1 links impaired autophagy and mitophagy to Alzheimer’s disease pathology
Pan, J., Wang, P.-J., Zhang, J., Knapskog, A., Watne, L. O., Wang, H.-L., Lagartos-Donate, M. J., Lautrup, S., Mao, L.-P., Wang, Q., et al. (2026) · Nature Aging · doi:10.1038/s43587-026-01108-z · Cited by 19 · see citing works
“Among the five mammalian Atg1 homologs (ULK1-4, STK36), ULK1 and ULK2 are 52% identical, sharing 78% homology within their protein kinase domains, and are functionally redundant in some conditions 56 .”
Meng, X., Li, H., Fang, E., Feng, J., & Zhao, X. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01411 · Cited by 18 · see citing works
“Two of them (ULK1 and ARNT) have been found to have important roles in regulating neuronal development: ULK1 is essential to mediate autophagy under nutrient-deficient conditions and regulate axon guidance in the developing forebrain of mouse via a non-canonical pathway (34, 35); ARNT is mostly expressed in neuronal c…”
Background
- Authors
- Lee, E.-J., & Tournier, C.
- Affiliations
- University of Manchester (GB)
- Corresponding author
- Tournier, Cathy
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2011-07
- Volume
- 7
- Issue
- 7
- Pages
- 689-695
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC3149696
- OpenAlex
- W1998147787
- Cited by
- 186
- References
- 0
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 11 · 2023: 10 · 2022: 15 · 2021: 20 · 2020: 11 · 2019: 17 · 2018: 13 · 2017: 13 · 2016: 13 · 2015: 12 · 2014: 10 · 2013: 10 · 2012: 3
- FWCI
- 6.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autophagy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Funders
- Wellcome Trust
- National Research Foundation
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- ULK1, ULK2, functional redundancy, nutrient deprivation, cerebellar granule cells, low potassium, cytoprotection, cell type specificity, fibroblasts
- MeSH terms
- Autophagy-Related Protein-1 Homolog, Animals, Autophagy, Cytoplasmic Granules, Embryo, Mammalian, Fibroblasts, Neurons, Potassium, Apoptosis, Protein Serine-Threonine Kinases, Mice, DNA Fragmentation
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