The overexpression of the cyclin-dependent kinase (CDK) inhibitor p21Waf1 can inhibit cell proliferation, which is mediated by direct binding to CDK and proliferating-cell nuclear antigen. In this study, we demonstrated that human cytosolic thymidine kinase 1 (TK1) polypeptide can form a complex with p21Waf1. The C-terminal domain of p21Waf1 appeared to interact with the TK1 polypeptide, but, despite the inhibitory function of p21Waf1, their association did not alter TK1 functional activity. However, overexpression of TK1 overcame p21Waf1-mediated growth suppression and blocked the association of CDK2 with p21Waf1, suggesting that TK1 interferes with the inhibitory function of p21Waf1. Based on these results, we here propose that the molecular function of p21Waf1 in cells can be perturbed through its interaction with another cellular protein, TK1.
- cell cycle
- cell growth
- protein interaction
Abbreviations used: TK, thymidine kinase; CDK, cyclin-dependent kinase; GST, glutathione S-transferase; PCNA, proliferating-cell nuclear antigen; HPV, human papillomavirus; Ni-NTA, Ni2+-nitrilotriacetate.
- The Biochemical Society, London ©2001