Ubp-M serine 552 phosphorylation by cyclin-dependent kinase 1 regulates cell cycle progression

Xu, Yang; Yang, Huirong; Joo, Heui-Yun; Yu, Jie; Smith, Anita; Schneider, David A.; Chow, Louise T.; Renfrow, Matthew B.; Wang, Hengbin

doi:10.4161/cc.26278

Cited by 13 publications

(27 citation statements)

References 38 publications

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“…Further analyses by in vitro phosphorylation assay and MS of peptides derived from proteins isolated from HeLa cells showed that S552 was the CDK1 phosphorylation site (Fig. S2, B and E), which was also reported recently ( Xu et al, 2013 ). Next, we treated HeLa cells with CDK1 inhibitor RO3306 and observed a significant reduction in Plk1–Usp16 interaction ( Fig.…”

Section: Resultssupporting

confidence: 86%

Usp16 regulates kinetochore localization of Plk1 to promote proper chromosome alignment in mitosis

Zhuo

Guo

Zhang

et al. 2015

Journal of Cell Biology

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Section: Resultssupporting

confidence: 86%

Usp16 regulates kinetochore localization of Plk1 to promote proper chromosome alignment in mitosis

Zhuo

Guo

Zhang

et al. 2015

Journal of Cell Biology

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“…55 Moreover, function of USP16 is controlled by phosphorylation of S552 by Cdk1 during mitosis. 56 Consistent with the proposed role of USP16 in chromatin deubiquitination, its catalytically inactive mutant USP16-C205S was reported to associate with mitotic chromatin. 57 Similarly, we have observed that catalytically inactive mutant USP3-C168S is enriched at chromatin during mitosis (data not shown).…”

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confidence: 60%

Polo-like kinase 1 inhibits DNA damage response during mitosis

et al. 2015

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Abbreviations: 53BP1, p53 binding protein 1; ATM, ataxia telangiectasia mutated kinase; BRCA1, breast cancer type 1 susceptibility protein; Cdk, cyclin dependent kinase; DDR, DNA damage response; Plk1, Polo-like kinase 1; H2AX, histone variant H2AX; IR -ionizing radiation; MDC1, mediator of DNA damage checkpoint protein 1; NCS -neocarzinostatin; NZ -nocodazole; PTIP, PAX transactivation activation domain-interacting protein; RIF1, Rap1-interacting factor 1 homolog; RNAi, RNA interference; RNF8, RING finger protein 8; RNF168, RING finger protein 168.In response to genotoxic stress, cells protect their genome integrity by activation of a conserved DNA damage response (DDR) pathway that coordinates DNA repair and progression through the cell cycle. Extensive modification of the chromatin flanking the DNA lesion by ATM kinase and RNF8/RNF168 ubiquitin ligases enables recruitment of various repair factors. Among them BRCA1 and 53BP1 are required for homologous recombination and nonhomologous end joining, respectively. Whereas mechanisms of DDR are relatively well understood in interphase cells, comparatively less is known about organization of DDR during mitosis. Although ATM can be activated in mitotic cells, 53BP1 is not recruited to the chromatin until cells exit mitosis. Here we report mitotic phosphorylation of 53BP1 by Plk1 and Cdk1 that impairs the ability of 53BP1 to bind the ubiquitinated H2A and to properly localize to the sites of DNA damage. Phosphorylation of 53BP1 at S1618 occurs at kinetochores and in cytosol and is restricted to mitotic cells. Interaction between 53BP1 and Plk1 depends on the activity of Cdk1. We propose that activity of Cdk1 and Plk1 allows spatiotemporally controlled suppression of 53BP1 function during mitosis.

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“…As previously discussed, Usp10 can deubiqutinate the mono-ubiquitinated H2A.Z variant of H2A which results in increased AR activity [ 14 ]. However, H2A can also be deubiquitinated by MYSM1 (2A-DUB) [ 26 ] and UbpM (Usp16) in a way that is independent of its phosphorylation by CDK1 [ 43 ], [ 44 ]. UbpM specifically deubiquitinates histone H2A, but not H2B.…”

Section: Regulation Of Epigenetics By Deubiquitinationmentioning

confidence: 99%

“…UbpM regulates the same checkpoint but via a different mechanism. Following S552 phosphorylation UbpM translocates to the nucleus and regulates the cell cycle G2/M phase progression and cell proliferation [ 44 ]. Additionally, Usp22 directly deubiquitinates TRF1 (TBP(TATA box-binding protein)-related factor 1) to regulate the transcription of cell cycle and apoptosis genes [ 60 ] and inhibits the transcriptional activity of p53 by deubiquitinating SIRT1 histone deacetylase [ 61 ] and by regulating MDMX stability [ 62 ].…”

Section: Regulation Of Epigenetics By Deubiquitinationmentioning

confidence: 99%

“…Phosphorylation of Usp10 by ATM is also required for Usp10 antioxidant activity in stress granules [ 69 ]. Phosphorylation of UbpM at Ser552 by cyclin-dependent kinase 1 (CDK1) is also needed for its translocation to the nucleus and regulation of the cell cycle G2/M phase progression and cell proliferation but, this phosphorylation is not required for its deubiquitinase activity, substrate specificity and regulation of gene expression [ 44 ]. Similarly, Usp7 short isoform (Usp7S) can be phosphorylated by CK2 at S18 leading to its protein stabilisation which subsequently increases the pool of MDM2 and decreases the levels of p53 protein [ 70 ].…”

Section: Regulation Of Epigenetics By Deubiquitinationmentioning

confidence: 99%

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Deubiquitinating enzymes as oncotargets

McClurg

Robson

2015

Oncotarget

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Carcinogenesis is a complex process tightly regulated at multiple levels by post-translational modifications. Epigenetics plays a major role in cancer development, all stable changes to the gene expression process that are not a result of a direct change in the DNA code are described as epigenetics. Epigenetic processes are regulated by post-translational modifications including ubiquitination which can directly affect either histones or transcription factors or may target their co-factors and interacting partners exerting an indirect effect. Deubiquitination of these target proteins is equally important and alterations in this pathway can also lead to cancer development, progression and metastasis. Only the correct, unaltered balance between ubiquitination and deubiquitination ensures healthy cellular homeostasis. In this review we focus on the role of deubiquitinating (DUB) enzymes in various aspects of epigenetics including the regulation of transcription factors, histone modifications, DNA damage repair pathways and cell cycle regulation. We discuss the impact of those processes on tumourigenesis and potential therapeutic applications of DUBs for cancer treatment.

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Ubp-M serine 552 phosphorylation by cyclin-dependent kinase 1 regulates cell cycle progression

Cited by 13 publications

References 38 publications

Usp16 regulates kinetochore localization of Plk1 to promote proper chromosome alignment in mitosis

Usp16 regulates kinetochore localization of Plk1 to promote proper chromosome alignment in mitosis

Polo-like kinase 1 inhibits DNA damage response during mitosis

Deubiquitinating enzymes as oncotargets

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