Return to search

VCP/p97 is required for the timely degradation of p27 in G0/G1 to S phase transition in MCF-7 cell

VCP/p97 works as a segregase to extract the ubiquitylated proteins from protein complexes, lipid membranes and chromosomes, thereby promoting their degradation or recycling. VCP/p97 plays essential roles in ubiquitin-dependent proteasome degradation, ERAD, autophagy, endocytosis, reassembly of ER, Golgi and nuclear envelop, and cell cycle regulation. In ubiquitin dependent proteasome degradation pathway, VCP/p97, as a special ubiquitin binding-shuttle factor, is required for the successful cell cycle progression in regulating IκB, CDT-1, Aurora B, and CDC25A. Here, we studied the role of VCP/p97 in G1 to S phase transition in MCF-7 human breast cancer cells. We found that VCP/p97 knockdown or inhibition by DBeQ, a potent VCP/p97 inhibitor, decreased cell proliferating rates and reduced S phase cell percentages in asynchronized MCF-7 cells.VCP/p97 inhibition by DBeQ also arrested cells at G1 phase in synchronized MCF-7 cells. These data suggest that VCP/p97 is required for G0/G1 to S phase transition in MCF-7 cells. In addition, in either asynchronized or synchronized MCF-7 cells, VCP/p97 knockdown or DBeQ treatment resulted in the accumulation of p21 and p27, two CDK inhibitors. Moreover, p27, not p21, knockdown in MCF-7 cells rescued the defects of S phase entry caused by VCP/p97 knockdown or DBeQ treatment. Taken together, our results suggest that VCP/p97 regulates the timely degradation of p27 to promote G1 to S phase transition in MCF-7 cells. / published_or_final_version / Physiology / Master / Master of Philosophy

Identiferoai:union.ndltd.org:HKU/oai:hub.hku.hk:10722/208005
Date January 2014
CreatorsShi, Xianli, 石现丽
ContributorsYue, J
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Source SetsHong Kong University Theses
LanguageEnglish
Detected LanguageEnglish
TypePG_Thesis
RightsCreative Commons: Attribution 3.0 Hong Kong License, The author retains all proprietary rights, (such as patent rights) and the right to use in future works.
RelationHKU Theses Online (HKUTO)

Page generated in 0.0018 seconds