BD Transduction Laboratories™ Purified Mouse Anti- TOK-1

Cell cycle progression is tightly regulated by the actions of cyclins and cyclin dependent kinases (Cdks). p21 forms a quaternary complex that includes Cyclin D, Cdk4, and PCNA, and is induced during p53-dependent and -independent responses to cellular stress. p21 promotes cell cycle arrest by preventing the phosphorylation and activation of Cdk. Although the Cdks are inhibited via direct interaction with the N-terminal region of p21, various other proteins bind the C-terminal region. TOK-1 is a p21 interacting protein that exists as 50 kDa (TOK-1α) and 45 kDa (TOK-1ß) isoforms. While both isoforms are primarily expressed in skeletal muscle, TOK-1ß is also expressed in a variety of other tissues, including placenta and pancreas. Although both isoforms localize to the nucleus, TOK-1α, not TOK-1ß, is coexpressed with p21 at the G1/S boundary and directly binds the C-terminal region of p21. TOK-1α has been shown to enhance the activity of p21,which inhibits the H1 kinase activity of Cdk2. In addition, the TOK proteins were identified as BCCIPα and BCCIPß, which are nuclear proteins that interact with BRCA2 and function in tumor suppression. Therefore, TOK-1 proteins may regulate cell cycle dynamics and cell transformation through a variety of protein-protein interactions.