VCP/p97 is required for the timely degradation of p27 in G0/G1 to S phase transition in MCF-7 cell
| Autor: | Shi, Xianli, 石现丽 |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: | |
| Druh dokumentu: | PG_Thesis |
| DOI: | 10.5353/th_b5351042 |
| Popis: | 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 |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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