The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
E4F1 Is an Atypical Ubiquitin Ligase that Modulates p53 Effector Functions Independently of Degradation
Open accessAbstract
p53 is regulated by multiple posttranslational modifications, including Hdm2-mediated ubiquitylation that drives its proteasomal degradation. Here, we identify the p53-associated factor E4F1, a ubiquitously expressed zinc-finger protein first identified as a cellular target of the viral oncoprotein E1A, as an atypical ubiquitin E3 ligase for p53 that modulates its effector functions without promoting proteolysis. E4F1 stimulates oligo-ubiquitylation in the hinge region of p53 on lysine residues distinct from those targeted by Hdm2 and previously described to be acetylated by the acetyltransferase PCAF. E4F1 and PCAF mediate mutually exclusive posttranslational modifications of p53. E4F1-dependent Ub-p53 conjugates are associated with chromatin, and their stimulation coincides with the induction of a p53-dependent transcriptional program specifically involved in cell cycle arrest, and not apoptosis. Collectively, our data reveal that E4F1 is a key posttranslational regulator of p53, which modulates its effector functions involved in alternative cell fates: growth arrest or apoptosis.
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Cites
Vogelstein, B., Lane, D., & Levine, A. J. (2000) · Nature · doi:10.1038/35042675 · Cited by 6,607 · cited 1×
“p53 is a key regulator of cell cycle control, apoptosis, and genomic stability in response to stress (Harris and Levine, 2005), and inactivation of the p53 pathway is a common feature of cancer cells (Vogelstein et al., 2000).”
Mdm2 promotes the rapid degradation of p53
Haupt, Y., Maya, R., Kazaz, A., & Oren, M. (1997) · Nature · doi:10.1038/387296a0 · Cited by 4,506
Regulation of p53 stability by Mdm2
Kubbutat, M. H. G., Jones, S. N., & Vousden, K. H. (1997) · Nature · doi:10.1038/387299a0 · Cited by 3,312 · cited 2×
“…between p53 and several ubiquitin (Ub) E3 ligases (Alarcon-Vargas and Ronai, 2002; Brooks and Gu, 2006), such as Hdm2/Mdm2 (Haupt et al., 1997; Kubbutat et al., 1997), E6-AP (Scheffner et al., 1993), Cop1 (Dornan et al., 2004), Pirh2 (Leng et al., 2003), and Mule/ARF-BP1 (Chen et al., 2005),…”
The p53 pathway: positive and negative feedback loops
Harris, S. L., & Levine, A. J. (2005) · Oncogene · doi:10.1038/sj.onc.1208615 · Cited by 1,967
Post-translational modification of p53 in tumorigenesis
Bode, A. M., & Dong, Z. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1455 · Cited by 1,270
DNA damage activates p53 through a phosphorylation–acetylation cascade
Sakaguchi, K., Herrera, J. E., Saito, S., Miki, T., Bustin, M., Vassilev, A., Anderson, C. W., & Appella, E. (1998) · Genes & Development · doi:10.1101/gad.12.18.2831 · Cited by 1,204
p53 ubiquitination: Mdm2 and beyond
Brooks, C. L., & Gu, W. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.01.020 · Cited by 924
Mono- Versus Polyubiquitination: Differential Control of p53 Fate by Mdm2
Li, M., Brooks, C. L., Wu-Baer, F., Chen, D., Baer, R., & Gu, W. (2003) · Science · doi:10.1126/science.1091362 · Cited by 804 · cited 4×
“Stimulation of Ub chain polymerization by Hdm2 was previously shown to depend on six lysines in the C terminus of human p53 (K370, K372, K373, K381, K382, and K386) (Krummel et al., 2005; Li et al., 2003; Nakamura et al., 2000; Rodriguez et al., 2000).”
Influentialp53 Sites Acetylated In Vitro by PCAF and p300 Are Acetylated In Vivo in Response to DNA Damage
Liu, L., Scolnick, D. M., Trievel, R. C., Zhang, H. B., Marmorstein, R., Halazonetis, T. D., & Berger, S. L. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.2.1202 · Cited by 776
MDM2–HDAC1-mediated deacetylation of p53 is required for its degradation
Ito, A., Kawaguchi, Y., Lai, C., Kovacs, J. J., Higashimoto, Y., Appella, E., & Yao, T. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf616 · Cited by 570
Cited by
Blinded by the Light: The Growing Complexity of p53
Vousden, K. H., & Prives, C. (2009) · Cell · doi:10.1016/j.cell.2009.04.037 · Cited by 3,163
Regulating the p53 pathway: in vitro hypotheses, in vivo veritas
Toledo, F., & Wahl, G. M. (2006) · Nature reviews. Cancer · doi:10.1038/nrc2012 · Cited by 1,286
Lysine Acetylation: Codified Crosstalk with Other Posttranslational Modifications
Yang, X.-J., & Seto, E. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.07.002 · Cited by 1,006
Acetylation of non-histone proteins modulates cellular signalling at multiple levels
Spange, S., Wagner, T., Heinzel, T., & Krämer, O. H. (2009) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2008.08.027 · Cited by 664
Polycomb Group Proteins: Multi-Faceted Regulators of Somatic Stem Cells and Cancer
Sauvageau, M., & Sauvageau, G. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.08.002 · Cited by 586
Metadata
- Authors
- Le Cam, L., Linares, L. K., Paul, C., Julien, E., Lacroix, M., Hatchi, E., Triboulet, R., Bossis, G., Shmueli, A., Rodriguez, M. S., Coux, O., & Sardet, C.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2006-11
- Volume
- 127
- Issue
- 4
- Pages
- 775-788
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2032076692
- Cited by
- 240
- References
- 10
- FWCI
- 10.08
- Type
- journal article
- Language
- en
- Open access
- bronze
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