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Structure and function of the oncoprotein related to liver cancer (Press Release)

Release Date
15 Feb, 2007
  • BL26B1 (RIKEN Structural Genomics I)

February 15, 2007

Gankyrin, which is an oncoprotein related to liver cancer, interacts with the tumor suppressor pRb (retinoblastoma protein) and enhances the degradation of pRb. However, the mechanism has been unknown so far. Gankyrin also interacts with S6 ATPase of the 19S regulatory particle of the 26S proteasome. Prof. Shigeyuki Yokoyama (the University of Tokyo / RIKEN), Dr. Balasundaram Padmanabhan (RIKEN), and coworkers determined the structure of gankyrin in complex with the C-terminal domain of S6 ATPase, by X-ray diffraction method using the RIKEN Structural Genomics I Beamline of SPring-8. The structural and biochemical analysis reveals that both pRb and S6 ATPase bind to gankyrin at the same site on gankyrin, the 182nd glutamic acid (E182), and that gankyrin interacts with pRb in both the presence and absence of S6 ATPase; however, the E182 residue in gankyrin is essential for the pRb interaction. These results suggest that a replacement between pRb and S6 ATPase can occur on gankyrin and may be a major cause of the aberrant cell growth of cancer by gankyrin. (Public Relations Office, JASRI/SPring-8) 
(links to a Japanese page)

"Structure of the Oncoprotein Gankyrin in Complex with S6 ATPase of the 26S Proteasome"
Yoshihiro Nakamura, Kazumi Nakano, Takashi Umehara, Mayumi Kimura, Yoshihide Hayashizaki, Akiko Tanaka, Masami Horikoshi, Balasundaram Padmanabhan, and Shigeyuki Yokoyama
Structure, Vol 15, 179-189, February 2007.