USP7 controls Chk1 protein stability by direct deubiquitination

Vega, Ignacio Alonso-de; Martín, Yusé; Smits, Veronique A. J.

doi:10.4161/15384101.2014.973324

Cited by 78 publications

(53 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, a recent study that investigated the function of RAD51AP1 in chicken DT‐40 cells has shown that RAD51AP1 does not only function in the repair of DSBs by homologous recombination, but also plays an important role during unperturbed replication and replication stress . We found that RAD51AP1 interacts with USP7, a DUB that has previously been shown to regulate the stability of Claspin and Chk1 after replication stress . Our finding that RAD51AP1 also interacts with USP7 during replication stress suggests that USP7 might have a general role in deubiquitylating proteins at stalled replication forks and thereby preventing their degradation through the proteasome.…”

Section: Discussionsupporting

confidence: 64%

“…B and C, Supporting Information Table 2). For instance, we have found that RAD51AP1 interacts with USP7, USP11, and USP1/UAF1 (WDR48) – DUBs that have been previously shown to play an important role in the cellular response to replication stress or DNA damage . Moreover, we have identified the interaction between RAD51AP1 and the ubiquitin ligase HUWE1 as well as the Cul4‐ubiquitin ligase substrate adaptor DDB1‐VPRBP (DCAF1).…”

Section: Resultsmentioning

confidence: 91%

See 1 more Smart Citation

ATR inhibition rewires cellular signaling networks induced by replication stress

et al. 2016

View full text Add to dashboard Cite

The slowing down or stalling of replication forks is commonly known as replication stress and arises from multiple causes such as DNA lesions, nucleotide depletion, RNA-DNA hybrids, and oncogene activation. The ataxia telangiectasia and Rad3-related kinase (ATR) plays an essential role in the cellular response to replication stress and inhibition of ATR has emerged as therapeutic strategy for the treatment of cancers that exhibit high levels of replication stress. However, the cellular signaling induced by replication stress and the substrate spectrum of ATR has not been systematically investigated. In this study, we employed quantitative MS-based proteomics to define the cellular signaling after nucleotide depletion-induced replication stress and replication fork collapse following ATR inhibition. We demonstrate that replication stress results in increased phosphorylation of a subset of proteins, many of which are involved in RNA splicing and transcription and have previously not been associated with the cellular replication stress response. Furthermore, our data reveal the ATR-dependent phosphorylation following replication stress and discover novel putative ATR target sites on MCM6, TOPBP1, RAD51AP1, and PSMD4. We establish that ATR inhibition rewires cellular signaling networks induced by replication stress and leads to the activation of the ATM-driven double-strand break repair signaling.

show abstract

Section: Discussionsupporting

confidence: 64%

Section: Resultsmentioning

confidence: 91%

ATR inhibition rewires cellular signaling networks induced by replication stress

et al. 2016

View full text Add to dashboard Cite

show abstract

“…USP1 and USP7 are reported to be involved in deubiquitination and stabilization of Chk1 [69, 70]. USP7 was also shown to regulate other DDR proteins such as Claspin, an adaptor protein activated by Chk1 in the ATR–Chk1 pathway [71].…”

Section: Dubs and Genomic Integritymentioning

confidence: 99%

The emerging role of deubiquitinating enzymes in genomic integrity, diseases, and therapeutics

Zhou

Shah

et al. 2016

Cell Biosci

View full text Add to dashboard Cite

The addition of mono-ubiquitin or poly-ubiquitin chain to signaling proteins in response to DNA damage signal is thought to be a critical event that facilitates the recognition of DNA damage lesion site, the activation of checkpoint function, termination and checkpoint response and the recruitment of DNA repair proteins. Despite the ubiquitin modifiers, removal of ubiquitin from the functional proteins by the deubiquitinating enzymes (DUBs) plays an important role in orchestrating DNA damage response as well as DNA repair processes. Deregulated ubiquitination and deubiquitination could lead to genome instability that in turn causes tumorigenesis. Recent TCGA study has further revealed the connection between mutations in alteration of DUBs and various types of tumors. In addition, emerging drug design based on DUBs provides a new avenue for anti-cancer therapy. In this review, we will summarize the role of deubiquitination and specificity of DUBs, and highlight the recent discoveries of DUBs in the modulation of ubiquitin-mediated DNA damage response and DNA damage repair. We will furthermore discuss the DUBs involved in the tumorigenesis as well as interception of deubiquitination as a novel strategy for anti-cancer therapy.

show abstract

“…It is also worth mentioning that deubiquitinases play a role in determining the stability of both claspin and Chk1. Thus, USP7 and USP29 contribute to determining claspin stability, whereas USP7 was recently shown to antagonize Chk1 ubiquitination . It therefore seems possible that regulation of these deubiquitinase activities might contribute to checkpoint regulation via claspin and Chk1.…”

Section: Chk1 Deactivationmentioning

confidence: 99%

DNA damage control: regulation and functions of checkpoint kinase 1

Smits

Gillespie

2015

The FEBS Journal

View full text Add to dashboard Cite

Checkpoint kinase 1 (Chk1) is a master regulator of the DNA damage and replication checkpoints in vertebrate cells. When activated via phosphorylation by its upstream regulatory kinase, ATR, Chk1 prevents cells with damaged or incompletely replicated DNA from entering mitosis, and acts to stabilize stalled replication forks and suppress replication origin firing when DNA synthesis is inhibited. Chk1 blocks mitosis by maintaining high levels of inhibitory tyrosine phosphorylation of the mitotic cyclin‐dependent kinase 1; however, the mechanisms that underlie replication fork stabilization and suppression of origin firing are less well defined. Although Chk1 function is evidently acutely regulated during these responses, how this occurs at the molecular level is incompletely understood. Recent evidence that Chk1 contains a ‘kinase‐associated 1’ domain within its regulatory C‐terminal region promises new insights. Additional modifications catalysed by other protein kinases, such as cyclin‐dependent kinase 1, Akt, and RSK, can combine with ubiquitylation to regulate Chk1 subcellular localization and protein stability. Interestingly, it is clear that Chk1 has less well‐defined functions in homologous recombination, chromatin modification, gene expression, spindle checkpoint proficiency, and cytokinesis. Here, we provide an overview of Chk1 regulation and functions, with an emphasis on unresolved questions that merit further research.

show abstract

USP7 controls Chk1 protein stability by direct deubiquitination

Cited by 78 publications

References 27 publications

ATR inhibition rewires cellular signaling networks induced by replication stress

ATR inhibition rewires cellular signaling networks induced by replication stress

The emerging role of deubiquitinating enzymes in genomic integrity, diseases, and therapeutics

DNA damage control: regulation and functions of checkpoint kinase 1

Contact Info

Product

Resources

About