Dissecting Roles of Ubiquitination in the p53 Pathway

Shan, Jing; Brooks, Chris; Kon, Ning; Li, M.; Gu, Wei

doi:10.1007/2789_2008_105

Cited by 12 publications

(11 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…USP7 is bound by at least two herpesvirus proteins (ICP0 and EBNA1) [22], [32] and has more recently emerged as a key regulator of the p53 tumour suppressor [43] and several other cellular proteins [44], [45], [46], [47]. USP7 can regulate the stability, function and even the sub-cellular localization of its substrates, in each case by virtue of its deubiquitylating activity.…”

Section: Discussionmentioning

confidence: 99%

The Herpesvirus Associated Ubiquitin Specific Protease, USP7, Is a Negative Regulator of PML Proteins and PML Nuclear Bodies

et al. 2011

View full text Add to dashboard Cite

The PML tumor suppressor is the founding component of the multiprotein nuclear structures known as PML nuclear bodies (PML-NBs), which control several cellular functions including apoptosis and antiviral effects. The ubiquitin specific protease USP7 (also called HAUSP) is known to associate with PML-NBs and to be a tight binding partner of two herpesvirus proteins that disrupt PML NBs. Here we investigated whether USP7 itself regulates PML-NBs. Silencing of USP7 was found to increase the number of PML-NBs, to increase the levels of PML protein and to inhibit PML polyubiquitylation in nasopharyngeal carcinoma cells. This effect of USP7 was independent of p53 as PML loss was observed in p53-null cells. PML-NBs disruption was induced by USP7 overexpression independently of its catalytic activity and was induced by either of the protein interaction domains of USP7, each of which localized to PML-NBs. USP7 also disrupted NBs formed from some single PML isoforms, most notably isoforms I and IV. CK2α and RNF4, which are known regulators of PML, were dispensable for USP7-associated PML-NB disruption. The results are consistent with a novel model of PML regulation where a deubiquitylase disrupts PML-NBs through recruitment of another cellular protein(s) to PML NBs, independently of its catalytic activity.

show abstract

Section: Discussionmentioning

confidence: 99%

The Herpesvirus Associated Ubiquitin Specific Protease, USP7, Is a Negative Regulator of PML Proteins and PML Nuclear Bodies

et al. 2011

View full text Add to dashboard Cite

show abstract

“…However, unlike Mdm2, Mdm4 (also known as MdmX), is devoid of autonomous E3 ligase activity. Another important regulator of p53 function is the Ubiquitin-Specific Protease 7, USP7 (OMIM 602519), which de-ubiquitylates p53 and protects it from proteasome-mediated degradation (Shan et al , 2008). The pivotal role of Mdm2 and Mdm4 in the control of p53 function supports the notion that polymorphisms at these loci might be potential modifiers of p53 function (Atwal et al , 2009).…”

Section: The Tp53 Gene Its Products and Regulationmentioning

confidence: 99%

The TP53 fertility network

et al. 2012

View full text Add to dashboard Cite

The TP53 gene, first described in 1979, was identified as a tumor suppressor gene in 1989, when it became clear that its product, the p53 nuclear phosphoprotein, was frequently inactivated in many different forms of cancers. Nicknamed “guardian of the genome”, TP53 occupies a central node in stress response networks. The p53 protein has a key role as transcription factor in limiting oncogenesis through several growth suppressive functions, such as initiating apoptosis, senescence, or cell cycle arrest. The p53 protein is directly inactivated in about 50% of all tumors as a result of somatic gene mutations or deletions, and over 80% of tumors demonstrate dysfunctional p53 signaling. Beyond the undeniable importance of p53 as a tumor suppressor, an increasing number of new functions for p53 have been reported, including its ability to regulate energy metabolism, to control autophagy, and to participate in various aspects of differentiation and development. Recently, studies on genetic variations in TP53 among different populations have led to the notion that the p53 protein might play an important role in regulating fertility. This review summarizes current knowledge on the basic functions of different genes of the TP53 family and TP53 pathway with respect to fertility. We also provide original analyses based on genomic and genotype databases, providing further insights into the possible roles of the TP53 pathway in human reproduction.

show abstract

“…There are over 100 DUBs in mammalian cells, belonging to five distinct families [4]. As is the case with ubiquitination, deubiquitination is a highly regulated process and has been implicated in many cellular functions including gene expression [7], DNA repair [8], cell cycle control [9], kinase activation [10], and apoptosis [11]. …”

Section: Introductionmentioning

confidence: 99%

Regulation of Abro1/KIAA0157 during myocardial infarction and cell death reveals a novel cardioprotective mechanism for Lys63-specific deubiquitination

Cilenti

Balakrishnan

Wang

et al. 2011

Journal of Molecular and Cellular Cardiology

View full text Add to dashboard Cite

Abro1 (also known as KIAA0157) is a scaffold protein that recruits polypeptides to assemble the BRISC (BRCC36-containing isopeptidase complex) deubiquitinating (DUB) enzyme. The four subunits of BRISC enzyme include Abro1, NBA1, BRE, and BRCC36 proteins. The DUB activity of the BRISC enzyme is exclusively directed against Lys63-linked polyubiquitin that does not have a proteolytic role but regulates protein function. In this report, we identified Abro1 as a specific interactor of THAP5, a zinc finger transcription factor that is involved in G2/M control and apoptosis. Abro1 was predominantly expressed in the heart and its protein level was regulated following experimentally induced myocardial ischemia/reperfusion (MI/R) injury. Furthermore, in patients with coronary artery disease (CAD), there was a dramatic increase in Abro1 protein level in the myocardial infarction (MI) area. Increase in Abro1 lead to a significant reduction in Lys63-linked ubiquitination of specific protein targets. Reducing the Abro1 protein level exacerbated cellular damage and cell death of cardiomyocytes due to MI/R injury. Additionally, overexpression of Abro1 in a heterologous system provided significant protection against oxidative stress-induced apoptosis. In conclusion, our results demonstrate that Abro1 protein level substantially increases in myocardial injury and coronary artery disease and this up-regulation is part of a novel cardioprotective mechanism. In addition, our data suggest a potential new link between Lys63-specific ubiquitination, its modulation by the BRISC DUB enzyme, and the development and progression of heart disease.

show abstract

Dissecting Roles of Ubiquitination in the p53 Pathway

Cited by 12 publications

References 20 publications

The Herpesvirus Associated Ubiquitin Specific Protease, USP7, Is a Negative Regulator of PML Proteins and PML Nuclear Bodies

The Herpesvirus Associated Ubiquitin Specific Protease, USP7, Is a Negative Regulator of PML Proteins and PML Nuclear Bodies

The TP53 fertility network

Regulation of Abro1/KIAA0157 during myocardial infarction and cell death reveals a novel cardioprotective mechanism for Lys63-specific deubiquitination

Contact Info

Product

Resources

About