HDACs and the epigenetic plasticity of cancer cells: Target the complexity

In the paper

“Here, the Sall4/Hdac2 complex represses their expression through an epigenetic switch involving the reduction of H3K27ac levels (Diener et al., 2021).”

What the sources say

• Supported

  The Discussion states that SALL4 and HDAC2 bind melanoma invasiveness genes and that SALL4 knockdown increases both H3K27 acetylation and their transcription. The Results section on differential histone acetylation likewise reports gained H3K27ac marks and increased transcription for invasiveness genes after knockdown, supporting the proposed repression mechanism. Page numbers are not provided in our copy. (LLM, conf=0.91)

  cites Diener et al., 2021 source

In the paper

“Consistent with this, silencing of HDAC3 promotes PD-L1 expression.”

What the sources say

• Supported

  The Results section ('HDAC3 inhibition promotes PD-L1 expression in B-cell lymphomas') reports that siRNA-mediated depletion of HDAC3 increased surface PD-L1 in A20 cells. This directly supports the claim in the B-cell lymphoma cells studied. (LLM, conf=0.94)

  cites Deng et al., 2019 source

In the paper

“In lung cancer, low levels of AMPK promote cell proliferation and tumour growth.”

What the sources say

• Partly supported

  The Results section (‘AMPK is associated with proliferation and metastasis of lung cancer’) reports that low AMPK expression slightly promoted proliferation in A549 and HBE cells. But in the A549 mouse xenograft experiment, tumour weight did not differ significantly between the low-AMPK and control groups, so the claim that low AMPK promotes tumour growth is not supported. (LLM, conf=0.91)

  cites Feng et al., 2020 sourceExperimental — accuracy not yet measured

In the paper

“This evidence is more relevant in neuroblastoma cells characterized by MYCN amplification (Thole et al., 2017).”

What the sources say

• Supported

  The Results section states that HDAC11 is important for neuroblastoma-cell viability with and without MYCN amplification, “particularly in the presence of MYCN amplification.” This supports the claim that the evidence is more relevant to MYCN-amplified cells. (LLM, conf=0.93)

  cites Thole et al., 2017 source

In the paper

“In addition, loss of Hdac11 promotes brown adipose tissue accumulation and function.”

What the sources say

• Partly supported

  The Results section on thermogenic potential reports increased UCP1 expression in brown adipose tissue (BAT) of HDAC11-knockout mice, and the Discussion says deletion promoted BAT thermogenic function. Neither section reports increased BAT accumulation; the reported reduction in tissue weight concerns white adipose tissue. (LLM, conf=0.86)

  cites Sun et al., 2018 sourceExperimental — accuracy not yet measured

In the paper

“It has been known for several years that HDAC11 negatively controls IL-10 transcriptional activity in antigen-presenting cells and regulates immune tolerance (Villagra et al., 2009).”

What the sources say

• Supported

  The Results section (‘Effects of HDAC11 overexpression in mouse and human APCs’) states that HDAC11 overexpression inhibited Il10 transcriptional activity in APCs, while inhibiting HDAC11 had the opposite effect. The Discussion identifies HDAC11 as a transcriptional repressor of Il10 in APCs and links it to APC-mediated immune activation versus tolerance. (LLM, conf=0.94)

  cites Villagra et al., 2009 source

In the paper

“HDAC1/2 deacetylate K518ac of GLI1 to allow its association with chromatin and activation of transcription (Canettieri et al., 2010).”

What the sources say

• Not checked yetcites Canettieri et al., 2010 source

In the paper

“HDAC2, together with HDAC3, can form a noncanonical complex with PACS-1 (phosphofurin acidic cluster sorting protein-1).”

What the sources say

• Not checked yetcites Mani et al., 2020 source

In the paper

“Lysine 85 of linker histone H1 is dynamically acetylated in response to DNA damage by the antagonistic activities of the acetyl-transferase p300/CBPassociated factor (PCAF/KAT2B) and HDAC1.”

What the sources say

• Not checked yetcites Li et al., 2018

In the paper

“For example, HDAC2, but not HDAC1 and HDAC6, represses the formation of primary cilia in pancreatic ductal carcinoma cells (Kobayashi et al., 2017).”

What the sources say

• Not checked yetcites Kobayashi et al., 2017 source

In the paper

“The use of HDAC inhibitors (HDACIs) in clinic, as single agent, is limited to few hematological tumors: the cutaneous T-cell lymphoma and the peripheral T-cell lymphoma (Bose, Dai and Grant, 2014;Moskowitz and Horwitz, 2017).”

What the sources say

• Not checked yetcites Bose, Dai and Grant, 2014
• Not checked yetcites Moskowitz and Horwitz, 2017

In the paper

“By deacetylating of H3K56, they promote NHEJ repair (Miller et al., 2010).”

What the sources say

• Not checked yetcites Miller et al., 2010 source

In the paper

“As a sensor, it coordinates signaling responses to environmental stimuli and its repression sustains cell proliferation (Peixoto, Richard, Pant, Biswas, & Gradilone, 2020).”

What the sources say

• Not checked yetcites Peixoto, Richard, Pant, Biswas, & Gradilone, 2020

In the paper

“IKAROS binds to the promoter of the anti-apoptotic gene BCL2L1/BCLXL where it recruits HDAC1, to repress transcription (Song et al., 2020).”

What the sources say

• Not checked yetcites Song et al., 2020

In the paper

“Focusing on a single target gene could lead to misinterpretation, as HDAC1/2 multiprotein complexes can also repress the expression of pro-apoptotic genes (Contreras et al., 2013;Piazza et al., 2013;Ramsey, He, Forster, Ory, & Ellisen, 2011).”

What the sources say

• Not checked yetcites Contreras et al., 2013 source
• Not checked yetcites Piazza et al., 2013 source
• Not checked yetcites Ramsey, He, Forster, Ory, & Ellisen, 2011

In the paper

“However, when the same GBM cells are transplanted in a different microenvironment in vivo, the absence of HDAC1 leads to a more aggressive/ invasive phenotype through activation of STAT3 (Lo Cascio et al., 2021).”

What the sources say

• Not checked yetcites Lo Cascio et al., 2021 source

In the paper

“The non-selective action of these inhibitors could be an explanation for the side effects, also severe, experienced by some patients.”

In the paper

“Consequently, impairment of HDAC1/2 activities both genetically and pharmacologically impairs cell proliferation and survival (Was et al., 2019).”

What the sources say

• Not checked yetcites Was et al., 2019 source

In the paper

“Within the CoREST complex, deubiquitylation of HDAC1 increases its interaction with SIN3 (Yang et al., 2020).”

What the sources say

• Not checked yetcites Yang et al., 2020 source

In the paper

“In GBM, silencing of HDAC1, but not HDAC2, profoundly affects proliferation of glioma stem cells by reactivating TP53 activities.”

What the sources say

• Not checked yetcites Lo Cascio et al., 2021 source

In the paper

“Epigenetic switching promotes MDSC differentiation into a more interstitial, macrophage-like phenotype.”

What the sources say

• Not checked yetcites Lu et al., 2020

In the paper

“In this context, HDAC2 plays the main role, independent of HDAC1.”

What the sources say

• Not checked yetcites Kumar et al., 2017 source

In the paper

“In the presence of entinostat, increased IFN-γ levels in the tumor microenvironment modulate the local cytokine landscape and promote antitumor myeloid polarization (Nguyen et al., 2018).”

What the sources say

• Not checked yetcites Nguyen et al., 2018 source

In the paper

“Entinostat was also identified as a potent inhibitor of regulatory activities responsible for immune-evasion and metastatic potential in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET).”

What the sources say

• Not checked yetcites Alvarez et al., 2018 source

In the paper

“A peculiar feature of HDAC3 is its interaction with nuclear receptor co-repressor 1 (NCOR1) and silencing mediator of retinoic acid and thyroid hormone receptor (SMRT/NCOR2) (Fig. 4).”

What the sources say

• Not checked yetcites Emmett & Lazar, 2019 source

In the paper

“For example, entinostat may increase the infiltration of MDSC (myeloid-derived suppressor cells) in the tumor microenvironment.”

What the sources say

• Not checked yetcites Kumar et al., 2017 source

In the paper

“Entinostat can suppress the immunosuppressive effect of tumorinfiltrating myeloid cells and reprogram them to eliminate antigennegative tumor cells.”

What the sources say

• Not checked yetcites Nguyen et al., 2018 source

In the paper

“Simply abrogating class I HDAC activity without any interference with other epigenetic regulators is sufficient to influence the expression of cytokines, chemokines, and other inflammatory signals that remodel immune cells activities (Hicks et al., 2020;Hicks et al., 2021;Nguyen et al., 2018).”

What the sources say

• Not checked yetcites Hicks et al., 2020 source
• Not checked yetcites Hicks et al., 2021 source
• Not checked yetcites Nguyen et al., 2018 source

In the paper

“In syngeneic mouse models of lung and renal cell carcinoma, entinostat alone inhibited the immunosuppressive function of both polymorphonuclear and monocytic-myeloid-derived suppressor cell populations (Orillion et al., 2017).”

What the sources say

• Not checked yetcites Orillion et al., 2017 source

In the paper

“Mutant TBL1XR1 shifts the repressive SMRT/HDAC3 complex from binding BCL6 to BACH2 TFs.”

What the sources say

• Not checked yetcites Venturutti et al., 2020 source

In the paper

“Cancer cells at the primary site can sculpture a pre-metastatic niche by releasing soluble factors and extracellular vesicles (Liu & Cao, 2016;Peinado et al., 2017).”

What the sources say

• Not checked yetcites Liu & Cao, 2016
• Not checked yetcites Peinado et al., 2017 source

In the paper

“A reprogramming that inhibits trafficking of MDSC through downregulation of CCR2 and CXCR2.”

What the sources say

• Not checked yetcites Lu et al., 2020

In the paper

“Indeed, knockdown of MIDEAS or DNTTIP1 in cancer cells leads to misalignment of chromosomes during mitosis.(Turnbull et al., 2020).”

What the sources say

• Not checked yetcites Turnbull et al., 2020 source

In the paper

“Genetic or pharmacological targeting of the CoREST complex enhances anti-tumour activity in mice (Bantscheff et al., 2011;Xiong et al., 2020).”

What the sources say

• Not checked yetcites Bantscheff et al., 2011 source
• Not checked yetcites Xiong et al., 2020 source

In the paper

“This study showed that a small group of patients benefited from the combined treatment.”

What the sources say

• Not checked yetcites Ny et al., 2021

In the paper

“Interestingly, low-dose adjuvant epigenetic therapy (a combination of the DNA methyltransferase inhibitor 5-azacytidine and entinostat) can disrupt the premetastatic microenvironment and inhibit both metastasis formation and growth.”

What the sources say

• Not checked yetcites Lu et al., 2020

In the paper

“Interestingly, somatic mutations of TBL1XR1 are observed in the most aggressive B-cell lymphomas.”

What the sources say

• Not checked yetcites Venturutti et al., 2020 source

In the paper

“However, the epigenetic repression exerted is dynamic and fully reversible.”

In the paper

“HDAC8 is subject to allosteric regulation, with populations moving back and forth between active and inactive states.”

What the sources say

• Not checked yetcites Lee, Rezai-Zadeh and Seto, 2004
• Not checked yetcites Millard et al., 2017 source
• Not checked yetcites Werbeck et al., 2020 source

In the paper

“In HDAC8, the presence of a tryptophan limits the available space in the foot pocket.”

What the sources say

• Not checked yetcites Millard et al., 2017 source
• Not checked yetcites Wang, Wiest, Helquist, Lan-Hargest, & Wiech, 2004
• Not checked yetcites Whitehead et al., 2011 source

In the paper

“Epigenetic independent activity of HDAC3 has been associated with breast cancer cell metastasis.”

What the sources say

• Not checked yetcites Zhang et al., 2017

In the paper

“CREBBP silencing in murine and human cells triggers the depletion of H3K27ac marks at enhancers and changes in gene expression that are very similar to signatures characterizing human lymphomas with CREBBP mutations.”

What the sources say

• Not checked yetcites Jiang et al., 2017 source

In the paper

“A similar effect of HDAC3 as an antagonist for the activation of enhancers involved in tumorigenesis has been observed in B-cell lymphomas (Höpken, 2017).”

What the sources say

• Not checked yetcites Höpken, 2017

In the paper

“A pro-oncogenic role of HDAC3 has also been identified in leukemogenesis.”

What the sources say

• Not checked yetcites Mehdipour et al., 2017 source

In the paper

“DNMT1 is required to maintain the proliferation of MM.”

What the sources say

• Not checked yetcites Harada et al., 2017 source

In the paper

“Its deletion reactivates the MYOD1-dependent myogenic program.”

What the sources say

• Not checked yetcites Phelps et al., 2016 source

In the paper

“It is important to note that these HATs can be coopted, in different cancer contexts, to sustain the transcriptional addiction required for cell fitness (Hogg et al., 2021).”

What the sources say

• Not checked yetcites Hogg et al., 2021 source

In the paper

“Mice deficient for Hdac3 do not develop because of defects at the gastrulation stage (Emmett & Lazar, 2019).”

What the sources say

• Not checked yetcites Emmett & Lazar, 2019 source

In the paper

“HDAC3 is recruited to critical enhancers via the BCL6/NCOR2 complex to promote lymphomagenesis (Jiang et al., 2017).”

What the sources say

• Not checked yetcites Jiang et al., 2017 source

In the paper

“An interplay that is also engaged as adaptive response to pan-HDACIs (Minisini et al., 2022).”

What the sources say

• Not checked yetcites Minisini et al., 2022 source

In the paper

“In multiple myeloma (MM), HDAC3 deacetylates DNMT1, thereby increasing its stability.”

What the sources say

• Not checked yetcites Harada et al., 2017 source

In the paper

“Another non-histone target of HDAC3 that plays a role in cancer is DNA methyltransferase 1 (DNMT1).”

What the sources say

• Not checked yetcites Harada et al., 2017 source

In the paper

“In colorectal carcinoma, CBX4 negatively regulates cancer metastasis by repressing RUNX2 transcription.”

What the sources say

• Not checked yetcites Wang et al., 2016

In the paper

“Moreover, down-modulation of Hdac3 or its inhibition supported the differentiation of PML-RARα-expressing cells (Mehdipour et al., 2017).”

What the sources say

• Not checked yetcites Mehdipour et al., 2017 source

In the paper

“A general antagonistic activity of the NCOR1/HDAC3 complex in regulating H3K27ac turnover at genomic loci under the supervision of CREBBP or EP300 was confirmed by additional studies (Basu et al., 2020).”

What the sources say

• Not checked yetcites Basu et al., 2020 source

In the paper

“The generation of tissue-specific deletions of Hdac3 in mice has revealed the critical role of this deacetylase in several contexts (Emmett & Lazar, 2019).”

What the sources say

• Not checked yetcites Emmett & Lazar, 2019 source

In the paper

“Interestingly, the downregulation of HDAC4, albeit to a lesser extent, also promoted the myogenic program (Phelps, Bailey, Vleeshouwer-Neumann, & Chen, 2016).”

What the sources say

• Not checked yetcites Phelps et al., 2016 source

In the paper

“In acute promyelocytic leukemia (APL), HDAC3 contributes to the repressive influence of the oncogenic fusion protein PML-RARα.”

What the sources say

• Not checked yetcites Mehdipour et al., 2017 source

In the paper

“Not surprisingly, HDAC3, similar to other HDACs and other epigenetic regulators, can exert antiproliferative effects.”

In the paper

“HDAC3 can deacetylate the Forkhead box (FoxO) TF FoxO3, due to the bridging function of the protein Geminin.”

What the sources say

• Not checked yetcites Zhang et al., 2017

In the paper

“In pediatric rhabdomyosarcomas the HDAC3/NCOR1/NCOR2 complex acts as a differentiation brake.”

What the sources say

• Not checked yetcites Phelps et al., 2016 source

In the paper

“Tumors in which, mutations that specifically inactivate HAT enzymatic activity are the driving oncogenic lesions, should benefit from treatment with isoform specific HDAC inhibitors.”

In the paper

“FoxO3 stimulates Dicer transcription and miRNA biogenesis.”

What the sources say

• Not checked yetcites Zhang et al., 2017

In the paper

“These cells preferentially return to the germinal center to drive lymphomagenesis.”

What the sources say

• Not checked yetcites Venturutti et al., 2020 source

In the paper

“Follicular lymphomas and diffuse large B-cell lymphomas frequently accumulate mutations in epigenetic regulators, including the HATs CREBBP and EP300 (Morin et al., 2011).”

What the sources say

• Not checked yetcites Morin et al., 2011 source

In the paper

“These CREBBP lymphomas strictly rely on HDAC3 to reduce H3K27ac signals.”

What the sources say

• Not checked yetcites Jiang et al., 2017 source

In the paper

“HDAC3 was identified by a CRISPR/Cas9-based phenotypic screen of class I and class II HDAC genes.”

What the sources say

• Not checked yetcites Phelps et al., 2016 source

In the paper

“For example, in complex with CBX4, HDAC3 may act as a tumor suppressor.”

What the sources say

• Not checked yetcites Wang et al., 2016

In the paper

“In principle, selective inhibition of HDAC3 could be therapeutic in rhabdomyosarcomas.”

In the paper

“Dicer level is critical for the metastatic process of breast cancer cells.”

What the sources say

• Not checked yetcites Zhang et al., 2017

In the paper

“Another non-histone target of HDAC3 is NICD1 (Notch1 intracellular domain).”

What the sources say

• Not checked yetcites Ferrante et al., 2020 source

In the paper

“HDAC3 is the only class I/II HDAC that promotes AKT phosphorylation.”

What the sources say

• Not checked yetcites Yan et al., 2018 source

In the paper

“In B-cell lymphomas, HDAC3 is recruited by BCL6 as part of a complex with NCOR1/NCOR2 to the PD -L1 promoter.”

What the sources say

• Not checked yetcites Deng et al., 2019 source

In the paper

“The PD-1/ PD-L1 axis is hijacked by cancer cells to counteract immune activation, allowing the tumor to escape the immune response.”

What the sources say

• Not checked yetcites Constantinidou et al., 2019 source

In the paper

“Preliminary studies have shown that HDAC3 affects genome instability.”

What the sources say

• Not checked yetcites Bhaskara et al., 2010 source

In the paper

“This result indicates an important mechanism of resistance to HDACIs therapy in vivo in PD-L1.”

In the paper

“These mutations lead to abnormal activation of the androgen receptor (AR) and AKT-mTORC1 signaling pathways (Blattner et al., 2017).”

What the sources say

• Not checked yetcites Blattner et al., 2017 source

In the paper

“In the presence of PD-L1, RGFP966 acted synergistically with anti PD-L1 therapy to suppress tumor growth (Deng et al., 2019).”

What the sources say

• Not checked yetcites Deng et al., 2019 source

In the paper

“Thus, inhibiting both HDAC3 and DNMT1 with their respective inhibitors will have a more potent anti-proliferative effect (Harada et al., 2017).”

What the sources say

• Not checked yetcites Harada et al., 2017 source

In the paper

“Also in this context, the use of a relatively specific HDAC3 inhibitor (RGFP966, Fig. 3) shows promising anti-tumor activities in a preclinical model of prostate cancer (Yan et al., 2018).”

What the sources say

• Not checked yetcites Yan et al., 2018 source

In the paper

“HDAC3 represses gene programs associated with CD8 T-cells differentiation and cytotoxicity, by buffering H3K27ac levels at relative promoters (Tay et al., 2020).”

What the sources say

• Not checked yetcites Tay et al., 2020

In the paper

“An addiction validated in primary patient-derived xenograft models of DLBCL (diffuse large B-cell lymphoma).”

What the sources say

• Not checked yetcites Mondello et al., 2020 source

In the paper

“As described above for DNMT1, HDAC3 deacetylates NICD1 and controls its stability to sustain Notch signaling (Ferrante et al., 2020).”

What the sources say

• Not checked yetcites Ferrante et al., 2020 source

In the paper

“Tip60 engagement is important to recruit other factors of the DDR (Mir et al., 2021).”

What the sources say

• Not checked yetcites Mir et al., 2021 source

In the paper

“The use of BRD4097 (Fig. 3), a new HDAC3selective inhibitor, (Wagner et al., 2016), confirmed the oncogenic addiction for HDAC3 in these tumors.”

What the sources say

• Not checked yetcites Wagner et al., 2016 source

In the paper

“More generally, upregulation of PD-L1 is a common feature of the response to HDACIs (Minisini et al., 2022).”

What the sources say

• Not checked yetcites Minisini et al., 2022 source

In the paper

“The role of the BCL6-HDAC3 axis as an important oncogenic element has been observed in B-cell lymphomas characterized by CREBBP mutations (Jiang et al., 2017).”

What the sources say

• Not checked yetcites Jiang et al., 2017 source

In the paper

“HDAC3 deacetylates lysine 14 and 20 of Akt (Long et al., 2017;Yan et al., 2018).”

What the sources say

• Not checked yetcites Long et al., 2017 source
• Not checked yetcites Yan et al., 2018 source

In the paper

“Since aberrant Notch signaling is critical for T-cell acute lymphoblastic leukemia (T-ALL) and chronic lymphocytic leukemia (CLL), these tumors represent other potential application of HDAC3-selective inhibitors (Fig. 3).”

In the paper

“Akt1 is another non-histone target of HDAC3 mediated deacetylation (Long et al., 2017;Yan et al., 2018).”

What the sources say

• Not checked yetcites Long et al., 2017 source
• Not checked yetcites Yan et al., 2018 source

In the paper

“The dynamics of H3K14 acetylation are important for the initiation of NER (Niida et al., 2018).”

What the sources say

• Not checked yetcites Niida et al., 2018 source

In the paper

“HDAC8 catalyzes the deacetylation of SMC3, which is required for efficient recycling of the cohesin complex (Deardorff et al., 2012).”

What the sources say

• Not checked yetcites Deardorff et al., 2012 source

In the paper

“Particularly critical is the deacetylation of SMAC3, which gives HDAC8 a critical and unique role in regulating cohesin function.”

What the sources say

• Not checked yetcites Deardorff et al., 2012 source

In the paper

“HDAC8 is frequently overexpressed in different tumor types (Lehmann et al., 2014;Moreno et al., 2010;Oehme et al., 2009).”

What the sources say

• Not checked yetcites Lehmann et al., 2014 source
• Not checked yetcites Moreno et al., 2010 source
• Not checked yetcites Oehme et al., 2009 source

In the paper

“In this way, HDAC8 inactivates TP53 by deacetylation.”

What the sources say

• Not checked yetcites Qi et al., 2015

In the paper

“Hdac8 is highly expressed in long-term hematopoietic stem cells (LT-HSCs).”

What the sources say

• Not checked yetcites Hua et al., 2017 source

In the paper

“More generally, HDAC8 affects cell proliferation in different tumor types (Vannini et al., 2004).”

What the sources say

• Not checked yetcites Vannini et al., 2004 source

In the paper

“Dysfunction or alteration of HDAC8, as well as its targeting by specific inhibitors, could have a broader effect via control of cohesin dynamics (Dasgupta, Antony, Braithwaite, & Horsfield, 2016;Yamauchi et al., 2011).”

What the sources say

• Not checked yetcites Dasgupta et al., 2016 source
• Not checked yetcites Yamauchi et al., 2011 source

In the paper

“Depletion of HDAC3 (but not HDAC1/2 or 6) potently cooperates with these inhibitors to kill melanoma cells.”

What the sources say

• Not checked yetcites Maertens et al., 2019 source

In the paper

“Remarkably, the CM fusion does not interact with other class I members.”

What the sources say

• Not checked yetcites Qi et al., 2015

In the paper

“The dynamics of H3K14ac may be critical for the temporal recruitment of elements of the repair machinery (Nishimoto et al., 2020).”

What the sources say

• Not checked yetcites Nishimoto et al., 2020 source

In the paper

“In AML, characterized by an inversion in chromosome 16, HDAC8 forms a complex with the fusion protein CBFB-SMMHC (CM) and TP53.”

What the sources say

• Not checked yetcites Qi et al., 2015

In the paper

“Consequently, hematopoietic progenitor cells defective in Hdac8 are impaired for long-term serial repopulation activity in vivo (Hua et al., 2017).”

What the sources say

• Not checked yetcites Hua et al., 2017 source

In the paper

“HDAC8 deacetylates also nonhistone proteins such as TP53 and ERR-α (Deardorff et al., 2012;Qi et al., 2015;Wilson, Tremblay, Deblois, Sylvain-Drolet, & Giguère, 2010;Yan et al., 2013).”

What the sources say

• Not checked yetcites Deardorff et al., 2012 source
• Not checked yetcites Qi et al., 2015
• Not checked yetcites Wilson et al., 2010 source

In the paper

“In breast cancer, TGF-β signaling correlates with stemness and metastasis via oligomerization of SMAD3/4.”

What the sources say

• Not checked yetcites Tang et al., 2020 source

In the paper

“The combination of quizartinib with the HDAC8 inhibitor 22d (Fig. 3), greatly reduces AML cell survival.”

What the sources say

• Not checked yetcites Long et al., 2020 source

In the paper

“Mechanistically, HDAC8 deacetylates c-Jun to enhance its transcriptional activity.”

What the sources say

• Not checked yetcites Emmons et al., 2019 source

In the paper

“HDAC7 has also been reported to be modulated during senescence and its downregulation promotes senescence in fibroblasts (Warnon et al., 2021).”

What the sources say

• Not checked yetcites Warnon et al., 2021 source

In the paper

“During RAS-induced senescence, artificial maintenance of HDAC4 levels can counteract cell cycle exit and reduce the expression of CDKN1A and CDKN2A, two important senescence markers.”