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Gankyrin regulates Retinoblastoma and p53 proteins

Choi, Myong-Ho; Park, Tae Jun
Department of Biochemistry & Molecular Biology
Gankyrin is a small protein (25kDa with 226 amino acids) that contains seven ankyrin repeats and is highly conserved. Gankyrin is a subunit of the 26S proteasome that specifically interacts with the S6b ATPase (also know as Rpt3) of the 19S regulator. The RB and p53 tumor suppressors lie at the heart of cancer biology, and inactivation of both pathways is seemingly essential for tumor development. Previous studies identified gankyrin as a component of the 26S proteasome that is consistently overexpressed in most of cancer and promotes cell transformation by binding RB. Gankyrin also binds MDM2 and facilitates its destruction of p53.

Cellular senescence is a program activated by normal cells in response to various types of stress. These include telomere uncapping, DNA damage, oxidative stress,

oncogene activity and others. p53 and Rb, have been shown to play critical roles in the induction of senescence. Both p53 and Rb are activated upon the entry into senescence. The p53 protein is stabilized and proceeds to activate its transcriptional targets, such as p21CIP1/WAF1. Rb is found at senescence in its active, hypophosphorylated form, in which it binds to the E2F protein family members to repress their transcriptional targets.
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