TSPY1 suppresses USP7-mediated p53 function and promotes spermatogonial proliferation

Cell Death & Disease
Ying ShenYuan Yang

Abstract

Testis-specific protein Y-linked 1 (TSPY1) is expressed predominantly in adult human spermatogonia and functions in the process of spermatogenesis; however, our understanding of the underlying mechanism is limited. Here we observed that TSPY1, as an interacting partner of TSPY-like 5 (TSPYL5), enhanced the competitive binding of TSPYL5 to ubiquitin-specific peptidase 7 (USP7) in conjunction with p53. This activity, together with its promotion of TSPYL5 expression by acting as a transcription factor, resulted in increased p53 ubiquitylation. Moreover, TSPY1 could decrease the p53 level by inducing the degradation of ubiquitinated USP7. We demonstrated that the promotion of p53 degradation by TSPY1 influenced the activity of p53 target molecules (CDK1, p21, and BAX) to expedite the G2/M phase transition and decrease cell apoptosis, accelerating cell proliferation. Taken together, the observations reveal the significance of TSPY1 as a suppressor of USP7-mediated p53 function in inhibiting p53-dependent cell proliferation arrest. By simulating TSPY1 function in Tspy1-deficient spermatogonia derived from mouse testes, we found that TSPY1 could promote spermatogonial proliferation by decreasing the Usp7-modulated p53 level. The findi...Continue Reading

References

Oct 6, 1995·Science·C M KnudsonS J Korsmeyer
Aug 1, 1995·The Journal of Cell Biology·D R KelloggA W Murray
Nov 1, 1996·Human Molecular Genetics·F SchniedersJ Schmidtke
Apr 16, 1998·The Journal of Biological Chemistry·G A McQuibbanP N Lewis
Sep 8, 1998·Cytogenetics and Cell Genetics·T VogelJ Schmidtke
Apr 14, 1999·Cell Death and Differentiation·T L BeumerD G de Rooij
Aug 3, 1999·European Journal of Biochemistry·T Krude
Jan 10, 2002·Journal of Andrology·Yizhong YinAbraham Morgentaler
Mar 22, 2002·Biology of Reproduction·Lonnie D RussellC Michael Knudson
Oct 23, 2002·Proceedings of the National Academy of Sciences of the United States of America·F Kent HamraDavid L Garbers
Aug 18, 2005·British Journal of Cancer·Y-H YinW-F Chen
Mar 15, 2006·Cell·Jennifer A Marshall Graves
Mar 29, 2008·Methods in Molecular Biology·F Kent HamraDavid L Garbers
Apr 11, 2008·International Journal of Andrology·Chris Tyler-Smith
Jul 24, 2008·International Journal of Cancer. Journal International Du Cancer·Tatsuo Kido, Yun-Fai Chris Lau
Feb 25, 2009·Nature Reviews. Cancer·Marcos Malumbres, Mariano Barbacid
Mar 24, 2009·Birth Defects Research. Part C, Embryo Today : Reviews·Yun-Fai Chris LauTatsuo Kido
Sep 24, 2009·The Journal of Clinical Endocrinology and Metabolism·Claudia GiachiniCsilla Krausz
Mar 20, 2010·Biology of Reproduction·Anja SchönerStephanie Schubert
Dec 21, 2010·Nature Cell Biology·Mirjam T EppingRené Bernards
Feb 22, 2012·Current Biology : CB·Dong ChenHaifan Lin
Nov 20, 2012·Current Opinion in Oncology·Noel A Warfel, Wafik S El-Deiry
Mar 4, 2014·Biochemical and Biophysical Research Communications·Tatsuo Kido, Yun-Fai Chris Lau

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Citations

Nov 25, 2018·Angiogenesis·Hee-Jun NaYee Sook Cho
Dec 11, 2020·Alzheimer's Research & Therapy·Yixuan ZhangHaochen Liu
Mar 7, 2021·International Journal of Molecular Sciences·Liting HuangSujie Zhu

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Methods Mentioned

BETA
two-hybrid
co-immunoprecipitation
Co-IP
transfection
flow cytometry
ChIP-PCR
immunoprecipitation
ubiquitination
biopsies
PCR

Software Mentioned

SPSS
BLAST Analysis Tool

Related Concepts

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