A novel role for the deubiquitinase USP1 in the control of centrosome duplication

Jung, Jin Ki; Jang, Seoyoung; Kim, Jung Min

doi:10.1080/15384101.2016.1138185

Cited by 10 publications

(9 citation statements)

References 45 publications

(58 reference statements)

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“…We showed that USP9X, through stabilizing CEP131, regulates centrosome duplication and mitotic fidelity. In addition to our study, numerous reports showed the involvement of deubiquitination enzymes including BAP1, USP33, USP1, USP44, CYLD and USP21 in centrosome regulation and chromosomal stability365354555657, supporting a notion that deubiquitinases are the key regulators in centrosome homeostasis and genome stability.…”

Section: Discussionsupporting

confidence: 88%

USP9X regulates centrosome duplication and promotes breast carcinogenesis

et al. 2017

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Defective centrosome duplication is implicated in microcephaly and primordial dwarfism as well as various ciliopathies and cancers. Yet, how the centrosome biogenesis is regulated remains poorly understood. Here we report that the X-linked deubiquitinase USP9X is physically associated with centriolar satellite protein CEP131, thereby stabilizing CEP131 through its deubiquitinase activity. We demonstrate that USP9X is an integral component of centrosome and is required for centrosome biogenesis. Loss-of-function of USP9X impairs centrosome duplication and gain-of-function of USP9X promotes centrosome amplification and chromosome instability. Significantly, USP9X is overexpressed in breast carcinomas, and its level of expression is correlated with that of CEP131 and higher histologic grades of breast cancer. Indeed, USP9X, through regulation of CEP131 abundance, promotes breast carcinogenesis. Our experiments identify USP9X as an important regulator of centrosome biogenesis and uncover a critical role for USP9X/CEP131 in breast carcinogenesis, supporting the pursuit of USP9X/CEP131 as potential targets for breast cancer intervention.

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Section: Discussionsupporting

confidence: 88%

USP9X regulates centrosome duplication and promotes breast carcinogenesis

et al. 2017

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“…We showed that USP9X is spatially restricted to the centrosome by PCM1 and CEP55 and regulates centrosome duplication in its catalytic activity-dependent manner, although it remains to be explored whether and how PCM1 or CEP55 contributes to USP9X-promoted centrosome biogenesis in the future. In addition to our finding, several studies reported that the deubiquitination enzymes including BAP1, USP33, USP1, USP44, cylindromatosis (CYLD), and USP21 have been implicated in centrosome regulation (43)(44)(45)(46)(47)(48), pointing to a role of deubiquitinases as key regulators in centrosome homeostasis. Possibly, PCM1 and/or CEP55 could be controlled by these enzymes.…”

Section: Discussionsupporting

confidence: 82%

The X-linked deubiquitinase USP9X is an integral component of centrosome

Wang

Tang

et al. 2017

Journal of Biological Chemistry

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The X-linked deubiquitinase USP9X has been implicated in multiple pathological disorders including malignancies and X-linked intellectual disability. However, its biological function and substrate repertoire remain to be investigated. In this study, we utilized the tandem mass tag labeling assay to identify USP9X-regulated proteins and revealed that the expression of multiple genes is altered in USP9X-deficient cells. Interestingly, we showed that USP9X promotes stabilization of centrosome proteins PCM1 and CEP55 through its catalytic activity. Remarkably, we demonstrated that USP9X is physically associated and spatially co-localized with PCM1 and CEP55 in the centrosome, and we revealed that either PCM1 or CEP55 loss resulted in impairment of USP9X centrosome localization. Moreover, we showed that USP9X is required for centrosome duplication, and this effect is dependent on its catalytic activity and its N-terminal module, which is responsible for physical association of USP9X with PCM1 and CEP55. Collectively, our experiments identified USP9X as an integral component of the centrosome where it functions to stabilize PCM1 and CEP55 and promote centrosome biogenesis.

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“…UAF1 constitutively binds to USP1, USP12, and USP46, and this binding greatly enhances their deubiquitinase activity. The UAF1/USP1 complex deubiquitinates a wide range of substrates and has been implicated in the regulation of DNA repair processes [15][16][17][18] , tumor pathogenesis [19][20][21][22][23] , and antiviral innate immunity 24 . USP1 can deubiquitinate and stabilize inhibitors of DNA binding proteins (IDs) and subsequently promote the maintenance of mesenchymal stem cells in osteosarcoma 6,15 .…”

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confidence: 99%

UAF1 deubiquitinase complexes facilitate NLRP3 inflammasome activation by promoting NLRP3 expression

Song

Zhao

et al. 2020

Nat Commun

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NOD-like receptor protein 3 (NLRP3) detects microbial infections or endogenous danger signals and activates the NLRP3 inflammasome, which has important functions in host defense and contributes to the pathogenesis of inflammatory diseases, and thereby needs to be tightly controlled. Deubiquitination of NLRP3 is considered a key step in NLRP3 inflammasome activation. However, the mechanisms by which deubiquitination controls NLRP3 inflammasome activation are unclear. Here, we show that the UAF1/USP1 deubiquitinase complex selectively removes K48-linked polyubiquitination of NLRP3 and suppresses its ubiquitination-mediated degradation, enhancing cellular NLRP3 levels, which are indispensable for subsequent NLRP3 inflammasome assembly and activation. In addition, the UAF1/USP12 and UAF1/USP46 complexes promote NF-κB activation, enhance the transcription of NLRP3 and proinflammatory cytokines (including pro-IL-1β, TNF, and IL-6) by inhibiting ubiquitination-mediated degradation of p65. Consequently, Uaf1 deficiency attenuates NLRP3 inflammasome activation and IL-1β secretion both in vitro and in vivo. Our study reveals that the UAF1 deubiquitinase complexes enhance NLRP3 and pro-IL-1β expression by targeting NLRP3 and p65 and licensing NLRP3 inflammasome activation.

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A novel role for the deubiquitinase USP1 in the control of centrosome duplication

Cited by 10 publications

References 45 publications

USP9X regulates centrosome duplication and promotes breast carcinogenesis

USP9X regulates centrosome duplication and promotes breast carcinogenesis

The X-linked deubiquitinase USP9X is an integral component of centrosome

UAF1 deubiquitinase complexes facilitate NLRP3 inflammasome activation by promoting NLRP3 expression

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