Browse

p31(comet) Induces Cellular Senescence through p21 Accumulation and Mad2 Disruption

Cited 19 time in Web of Science Cited 18 time in Scopus
Authors
Yun, Miyong; Han, Young-Hoon; Yoon, Sun Hee; Kim, Hee Young; Kim, Bu-Yeo; Ju, Yeun-Jin; Kang, Chang-Mo; Jang, Su Hwa; Chung, Hee-Yong; Lee, Su-Jae; Cho, Myung-Haing; Yoon, Gyesoon; Park, Gil Hong; Kim, Sang Hoon; Lee, Kee-Ho
Issue Date
2009-03
Citation
Molecular Cancer Research, Vol.7 No.3, pp.371-382
Abstract
Functional suppression of spindle checkpoint protein activity results in apoptotic cell death arising from mitotic failure, Including defective spindle formation, chromosome missegregation, and premature mitotic exit. The recently identified p31(comet) protein acts as a spindle checkpoint silencer via communication with the transient Mad2 complex. In the present study, we found that p31(comet) overexpression led to two distinct phenotypic changes, cellular apoptosis and senescence. Because of a paucity of direct molecular link of spindle checkpoint to cellular senescence, however, the present report focuses on the relationship between abnormal spindle checkpoint formation and p31(comet)-induced senescence by using susceptible tumor cell lines. p31(comet)-Induced senescence was accompanied by mitotic catastrophe with massive nuclear and chromosomal abnormalities. The progression of the senescence was completely inhibited by the depletion of p21(Waf1/Clp1) and partly Inhibited by the depletion of the tumor suppressor protein p53. Notably, p21(Waf1/Clp1) depletion caused a dramatic phenotypic conversion of p31(comet)-induced senescence Into cell death through mitotic catastrophe, indicating that p21(Waf1/Clp1) major mediator of p31(comet)-induced cellular senescence. In contrast to wild-type p31(comet), overexpression of a p31 mutant lacking the Mad2 binding region did not cause senescence. Moreover, depletion of Mad2 by small interfering RNA induced senescence. Here, we show that p31(comet) Induces tumor cell senescence by mediating p21(Waf1/Clp1) accumulation and Mad2 disruption and that these effects are dependent on a direct interaction of p31(comet) with Mad2. Our results could be used to control tumor growth. (Mol Cancer Res 2009;7(3):371-82)
ISSN
1541-7786
URI
https://hdl.handle.net/10371/172470
DOI
https://doi.org/10.1158/1541-7786.MCR-08-0056
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Veterinary Medicine (수의과대학)Dept. of Veterinary Medicine (수의학과)Journal Papers (저널논문_수의학과)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse