Gankyrin: a new oncoprotein and regulator of pRb and p53

被引:79
作者
Dawson, Simon
Higashitsuji, Hiroaki
Wilkinson, Anthony J.
Fujita, Jun
Mayer, R. John [1 ]
机构
[1] Univ Nottingham, Sch Med, Queens Med Ctr, Sch Biomed Sci, Nottingham NG7 2UH, England
[2] Kyoto Univ, Grad Sch Med, Dept Clin Mol Biol, Sakyo Ku, Kyoto 6068507, Japan
[3] Univ York, Dept Chem, Struct Biol Lab, York YO10 5YW, N Yorkshire, England
基金
日本学术振兴会; 英国生物技术与生命科学研究理事会;
关键词
D O I
10.1016/j.tcb.2006.03.001
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Gankyrin is a new oncoprotein with potent cell cycle and apoptotic properties that is overexpressed early in hepatocarcinogenesis and in hepatocellular carcinomas. Gankyrin regulates the phosphorylation of the retinoblastoma protein (pRb) by CDK4 and enhances the ubiquitylation of p53 by the RING ubiquitin ligase MDM2. Purified preparations of the 26S proteasome contain gankyrin, which specifically interacts with the S6b (Rpt3) ATPase of the 19S regulator. In conclusion, gankyrin is a small versatile cell cycle regulator that illustrates the essential interplay between the ubiquitin proteasome system and gene expression in the cell. Here, we discuss the activities of gankyrin and present a model for its function in the regulation of pRb and p53.
引用
收藏
页码:229 / 233
页数:5
相关论文
共 46 条
[11]   DSS1 is required for RAD51 focus formation and genomic stability in mammalian cells [J].
Gudmundsdottir, K ;
Lord, CJ ;
Witt, E ;
Tutt, ANJ ;
Ashworth, A .
EMBO REPORTS, 2004, 5 (10) :989-993
[12]   Crystal structure of ClpA, an Hsp100 chaperone and regulator of ClpAP protease [J].
Guo, FS ;
Maurizi, MR ;
Esser, L ;
Xia, D .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (48) :46743-46752
[13]   Imbalance in liver homeostasis leading to hyperplasia by overexpressing the Bcl-2-related genes, zfBLP1 either one of and zfMcl-1a [J].
Her, GM ;
Cheng, CH ;
Hong, JR ;
Sundaram, GS ;
Wu, JL .
DEVELOPMENTAL DYNAMICS, 2006, 235 (02) :515-523
[14]   The oncoprotein gankyrin binds to MDM2/HDM2, enhancing ubiquitylation and degradation of p53 [J].
Higashitsuji, H ;
Higashitsuji, H ;
Itoh, K ;
Sakurai, T ;
Nagao, T ;
Sumitomo, H ;
Masuda, T ;
Dawson, S ;
Shimada, Y ;
Mayer, RJ ;
Fujita, J .
CANCER CELL, 2005, 8 (01) :75-87
[15]   Reduced stability of retinoblastoma protein by gankyrin, an oncogenic ankyrin-repeat protein overexpressed in hepatomas [J].
Higashitsuji, H ;
Itoh, K ;
Nagao, T ;
Dawson, S ;
Nonoguchi, K ;
Kido, T ;
Mayer, RJ ;
Arii, S ;
Fujita, J .
NATURE MEDICINE, 2000, 6 (01) :96-99
[16]   cDNA cloning and functional analysis of p28 (Nas6p) and p40.5 (Nas7p), two novel regulatory subunits of the 26S proteasome [J].
Hori, T ;
Kato, S ;
Saeki, M ;
DeMartino, GN ;
Slaughter, CA ;
Takeuchi, J ;
Toh-e, A ;
Tanaka, K .
GENE, 1998, 216 (01) :113-122
[17]   Fission yeast DSS1 associates with the proteasome and is required for efficient ubiquitin-dependent proteolysis [J].
Jossé, L ;
Harley, ME ;
Pires, IMS ;
Hughes, DA .
BIOCHEMICAL JOURNAL, 2006, 393 (01) :303-309
[18]   The BRCA2-interacting protein DSS1 is vital for DNA repair, recombination, and genome stability in Ustilago maydis [J].
Kojic, M ;
Yang, HJ ;
Kostrub, CF ;
Pavletich, NP ;
Holloman, WK .
MOLECULAR CELL, 2003, 12 (04) :1043-1049
[19]   Proteasome involvement in the repair of DNA double-strand breaks [J].
Krogan, NJ ;
Lam, MHY ;
Fillingham, J ;
Keogh, MC ;
Gebbia, M ;
Li, J ;
Datta, N ;
Cagney, G ;
Buratowski, S ;
Emili, A ;
Greenblatt, JF .
MOLECULAR CELL, 2004, 16 (06) :1027-1034
[20]   The C-terminal lysines fine-tune P53 stress responses in a mouse model but are not required for stability control or transactivation [J].
Krummel, KA ;
Lee, CJ ;
Toledo, F ;
Wahl, GM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (29) :10188-10193