2009
DOI: 10.1038/onc.2009.427
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Inactivation of HAUSP in vivo modulates p53 function

Abstract: Hausp is a deubiquitinase that has been shown to regulate the p53-Mdm2 pathway. Cotransfection of p53 and Hausp stabilizes p53 through the removal of ubiquitin moieties from polyubiquitinated p53. Interestingly, knockout or RNA interference-mediated knockdown of Hausp in human cells also resulted in the stabilization of p53 due to the destabilization of Mdm2, suggesting a dynamic role of Hausp in p53 activation. To understand the physiological functions of Hausp, we generated hausp knockout mice. Hausp knockou… Show more

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Cited by 170 publications
(176 citation statements)
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References 32 publications
(35 reference statements)
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“…USP7 knockout mice display early lethality (E3.5); USP7 À / À cells are characterized by the loss of MDM2, accumulation of p53, proliferation arrest and apoptosis. 46 However, deletion of p53 gene in a USP7 knockout mouse background did not rescue embryonic lethality (contrary to what was shown for MDM2 knockout mice 47 ), highlighting the importance of p53-independent functions of USP7. 46,48 We demonstrated that depletion of USP7 delays early mitotic events leading to the accumulation of cells in prometa/ metaphases (Figure 3), confirmed by cyclin B stabilization ( Figure 2) as was shown for Daxx.…”
Section: Discussionmentioning
confidence: 79%
See 1 more Smart Citation
“…USP7 knockout mice display early lethality (E3.5); USP7 À / À cells are characterized by the loss of MDM2, accumulation of p53, proliferation arrest and apoptosis. 46 However, deletion of p53 gene in a USP7 knockout mouse background did not rescue embryonic lethality (contrary to what was shown for MDM2 knockout mice 47 ), highlighting the importance of p53-independent functions of USP7. 46,48 We demonstrated that depletion of USP7 delays early mitotic events leading to the accumulation of cells in prometa/ metaphases (Figure 3), confirmed by cyclin B stabilization ( Figure 2) as was shown for Daxx.…”
Section: Discussionmentioning
confidence: 79%
“…46 However, deletion of p53 gene in a USP7 knockout mouse background did not rescue embryonic lethality (contrary to what was shown for MDM2 knockout mice 47 ), highlighting the importance of p53-independent functions of USP7. 46,48 We demonstrated that depletion of USP7 delays early mitotic events leading to the accumulation of cells in prometa/ metaphases (Figure 3), confirmed by cyclin B stabilization ( Figure 2) as was shown for Daxx. 20,21 Results were reproduced in p53-null cells, excluding indirect effect of USP7 on mitosis via stabilization of p53 (Figures 2d and 3b and Supplementary Figure S2).…”
Section: Discussionmentioning
confidence: 79%
“…However, it is possible that the ZnF-UBP domain also presents a protein interaction module for the 72 other human proteins which possess COOH-terminal di-Gly motifs. One interesting member of this list is histone H4, which could serve to recruit both USP3 and USP16 to histone complexes, where they have been proposed to deubiquitylate histone H2A (87,110,183 p53 activation, as embryonic development is extended in USP7/p53 double-knockout embryos (124,125).…”
Section: A Usp Familymentioning
confidence: 99%
“…So far, USP2, USP4, USP5, USP7, USP10 and USP29 have been described to participate in p53 regulation. USP7 is involved in the dynamic control of the p53-MDM2 pathway by regulating the stability of both p53 and MDM2, a ubiquitin ligase that also contributes to the maintenance of p53 ubiquitylation levels (Brooks et al, 2007;Kon et al, 2010). Hence, USP7 can be considered as an oncogene or a tumor suppressor depending on whether it predominantly deubiquitylates MDM2 or p53, respectively.…”
Section: Signaling Pathwaysmentioning
confidence: 99%
“…Further studies have shown that several DUBs may function either as oncogenes or tumor suppressors depending on the cellular context. In fact, there are DUBs with dual roles as pro-tumorigenic and antitumorigenic enzymes depending on the target affected by their regulation, as discussed above for USP7, CYLD and A20 (Vendrell et al, 2007;Stegmeier et al, 2007b;Kon et al, 2010).…”
Section: Genetic or Functional Alterations Of Dubs In Cancermentioning
confidence: 99%