Histone Deacetylase 3 Regulates Cyclin A Stability

Vidal-Laliena, Miriam; Gallastegui, Edurne; Mateo, Francesca; Martínez‐Balbás, Marian A.; Pujol, María Jesús; Bachs, Oriol

doi:10.1074/jbc.m113.458323

Cited by 28 publications

(28 citation statements)

References 38 publications

(54 reference statements)

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“…In yeast, CDK1 can be acetylated at lysine 33, which is essential for proper growth (32). Moreover, a recent study using HeLa cells showed that HDAC3 deacetylates and prevents the ubiquitination of cyclin A (14). However, in our study, although we detected acetylated CDK1 in HCN cells, we did not observe any differences in CDK1 acetylation levels after HDAC3 inhibition or overexpression, possibly due to regulation by other HDACs.…”

Section: Discussioncontrasting

confidence: 56%

“…The discrepancies in cell cycle defects after loss of HDAC3 may reflect alterations in the level of HDAC3 at different stages of the cell cycle. For instance, in HeLa cells, the levels of HDAC3 are reduced in metaphase due to proteasome degradation (14). However, in NSPCs, we observed consistently high levels of HDAC3 throughout the cell cycle (Fig.…”

Section: Discussionmentioning

confidence: 65%

“…Previous studies showed that HDAC3 could regulate the G1/S phase transition in HeLa cells (14), but was only required for S-phase progression in mouse embryonic fibroblast (MEF) cells (18), suggesting that HDAC3 has distinct roles on cell cycle progression in different cell types. To gain further insight into the role of HDAC3 in NSPC proliferation, specifically, in regulating cell cycle progression, we performed cell cycle analysis following propidium iodide staining of WT and Hdac3 floxed neurospheres.…”

Section: Significancementioning

confidence: 99%

“…In human colon cancer cells, HDAC3 levels are elevated, which have been suggested to control cells in both S and gap 2/mitosis (G2/M) phase (12). Loss of HDAC3 in hematopoietic progenitor cells results in only S-phase progression defects (13), whereas in HeLa cells, a G1/S transition defect was observed after knockdown of HDAC3 (14). However, the underlying mechanisms are still unclear; in particular, which stage(s) of cell cycle HDAC3 control(s) in NSPCs.…”

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confidence: 99%

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HDAC3 controls gap 2/mitosis progression in adult neural stem/progenitor cells by regulating CDK1 levels

Jiang

Hsieh

2014

Proc. Natl. Acad. Sci. U.S.A.

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The maintenance of the resident adult neural stem/progenitor cell (NSPC) pool depends on the precise balance of proliferation, differentiation, and maintenance of the undifferentiated state. Identifying the mechanisms that regulate this balance in adult hippocampal NSPCs can provide insight into basic stem cell selfrenewal principles important for tissue homeostasis and preventing tumor formation. Pharmacological inhibition of histone deacetylases (HDACs), a class of histone-modifying enzymes, have promising effects in cancer cells, yet the specific roles of individual HDACs in stem cell proliferation is unclear. Here using conditional KO (cKO) mice and in vitro cell culture, we show that histone deacetylase 3 (HDAC3) is required for the proliferation of adult NSPCs. Detailed cell cycle analysis of NSPCs from Hdac3 cKO mice reveals a defect in cell cycle progression through the gap 2/mitosis (G2/M) but not the S phase. Moreover, HDAC3 controls G2/M phase progression mainly through posttranslational stabilization of the G2/M cyclindependent kinase 1 (CDK1). These results demonstrate that HDAC3 plays a critical role in NSPC proliferation and suggest that strategies aimed at pharmacological modulation of HDAC3 may be beneficial for tissue regeneration and controlling tumor cell growth.adult hippocampal neurogenesis | epigenetic | acetylation | ubiquitination | malignancy

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Section: Discussioncontrasting

confidence: 56%

Section: Discussionmentioning

confidence: 65%

Section: Significancementioning

confidence: 99%

mentioning

confidence: 99%

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HDAC3 controls gap 2/mitosis progression in adult neural stem/progenitor cells by regulating CDK1 levels

Jiang

Hsieh

2014

Proc. Natl. Acad. Sci. U.S.A.

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“…An abrupt loss of HDAC3 at metaphase facilitates cyclin A acetylation by PCAF/GCN5, which target cyclin A for degradation. Because cyclin A is crucial for S-phase progression and entry into mitosis, HDAC3 knockdown causes cell accumulation in the S and G 2 /M phases (20).…”

mentioning

confidence: 99%

Histone Deacetylase 10 Regulates the Cell Cycle G₂/M Phase Transition via a Novel Let-7–HMGA2–Cyclin A2 Pathway

Peng

Seto

2015

Molecular and Cellular Biology

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Histone deacetylase (HDAC) inhibition leads to cell cycle arrest in G 1 and G 2 , suggesting HDACs as therapeutic targets for cancer and diseases linked to abnormal cell growth and proliferation. Many HDACs are transcriptional repressors. Some may alter cell cycle progression by deacetylating histones and repressing transcription of key cell cycle regulatory genes. Here, we report that HDAC10 regulates the cell cycle via modulation of cyclin A2 expression, and cyclin A2 overexpression rescues HDAC10 knockdown-induced G 2 /M transition arrest. HDAC10 regulates cyclin A2 expression by deacetylating histones near the let-7 promoter, thereby repressing transcription. In HDAC10 knockdown cells, let-7f and microRNA 98 (miR-98) were upregulated and the let-7 family target, HMGA2, was downregulated. HMGA2 loss resulted in enrichment of the transcriptional repressor E4F at the cyclin A2 promoter. These findings support a role for HDACs in cell cycle regulation, reveal a novel mechanism of HDAC10 action, and extend the potential of HDACs as targets in diseases of cell cycle dysregulation. Histone function is modulated by several posttranslational modifications, including reversible acetylation of the N-terminal ε-group of lysines on histones (1). Histone acetylation is tightly controlled by a balance between the opposing activities of histone acetyltransferases and histone deacetylases (HDACs). Acetylation of histone core molecules modulates chromatin structure and gene expression (2). The human HDAC family includes 18 members grouped into four classes. Class I HDACs, orthologs of Saccharomyces cerevisiae RPD3, are comprised of HDAC1, -2, -3, and -8. Class II, similar to yeast HDA1, has two subclasses: IIa (HDAC4, -5, -6, -7, and -9) and IIb (HDAC6 and -10). Class III, related to yeast SIR2, consists of seven sirtuins, which require NAD ϩ for activity. Class IV contains only HDAC11, which shows limited homologies to class I and II enzymes. Whereas class III HDACs are inhibited by nicotinamide, class I and II HDACs are dependent on Zn 2ϩ for deacetylase activity. The class IIb HDAC6 and HDAC10 are specifically sensitive to hydroxamate-type inhibitors (3), such as trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA). Most hydroxamate inhibitors are nonselective, with the exception of tubacin and tabastatin A, which are selective for HDAC6 (4, 5). Another hydroxamate compound, bufexamac, also has been identified as a novel class IIb inhibitor that specifically inhibits HDAC6 at lower doses (3, 6). In addition, the cellular acetylome regulated by HDAC6 correlated with the profile observed after bufexamac treatment (6). However, the effect and mechanism of bufexamac on HDAC10 have not yet been well-studied. Thus, identification of the catalytic structure and mechanism of action of HDAC10 might inform the development of a selective inhibitor in future research.HDACs play important roles in the regulation of the cell cycle, apoptosis, stress responses, and DNA repair, indicating that they are key regulators of normal ...

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Depletion of HOXA5 inhibits the osteogenic differentiation and proliferation potential of stem cells from the apical papilla

Xiao

Yang

et al. 2017

Cell Biology International

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Mesenchymal stem cells (MSCs) are a prospective cell source for tissue regeneration due to their self-renewal abilities and potential to differentiate into different cell lineages, but the molecular mechanisms of the directed differentiation and proliferation are still unknown. Recently, multiple studies have indicated the crucial role of HOX genes in MSC differentiation and proliferation. However, the role of HOXA5 in MSCs remains unknown. Here, we investigated HOXA5 function in stem cells from the apical papilla (SCAPs). After HOXA5 depletion, the results showed a significant decrease in ALP activity and a weakened mineralization ability of SCAPs. The real-time RT-PCR results showed prominently lessened expression of OPN and BSP. The CCK8 and CFSE results displayed inhibited proliferation of SCAPs, and flow cytometry assays revealed arrested cell cycle progression at the S phase. Furthermore, we found that depletion of HOXA5 upregulated p16 INK4A and p18 INK4C and downregulated the Cyclin A. Our research demonstrated that depletion of HOXA5 inhibited osteogenic differentiation and repressed cell proliferation by arresting cell cycle progression at the S phase via p16 INK4A , p18 INK4C , and Cyclin A in SCAPs, indicating that HOXA5 has a significant role in maintaining the proliferation and differentiation potential of dental-tissue-derived MSCs.

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Histone Deacetylase 3 Regulates Cyclin A Stability

Cited by 28 publications

References 38 publications

HDAC3 controls gap 2/mitosis progression in adult neural stem/progenitor cells by regulating CDK1 levels

HDAC3 controls gap 2/mitosis progression in adult neural stem/progenitor cells by regulating CDK1 levels

Histone Deacetylase 10 Regulates the Cell Cycle G₂/M Phase Transition via a Novel Let-7–HMGA2–Cyclin A2 Pathway

Depletion of HOXA5 inhibits the osteogenic differentiation and proliferation potential of stem cells from the apical papilla

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Histone Deacetylase 3 Regulates Cyclin A Stability

Cited by 28 publications

References 38 publications

HDAC3 controls gap 2/mitosis progression in adult neural stem/progenitor cells by regulating CDK1 levels

HDAC3 controls gap 2/mitosis progression in adult neural stem/progenitor cells by regulating CDK1 levels

Histone Deacetylase 10 Regulates the Cell Cycle G2/M Phase Transition via a Novel Let-7–HMGA2–Cyclin A2 Pathway

Depletion of HOXA5 inhibits the osteogenic differentiation and proliferation potential of stem cells from the apical papilla

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Histone Deacetylase 10 Regulates the Cell Cycle G₂/M Phase Transition via a Novel Let-7–HMGA2–Cyclin A2 Pathway