Binding domain for p21(WAF1) on the polypeptide chain of the protein kinase CK2 beta-subunit

Protein kinase CK2 is a ubiquitous serine/threonine kinase which is involve d in many proliferation-related processes in the cell. Id is composed of tw o regulatory beta-subunits and two catalytic alpha-subunits. Its regulation still remains mysterious in spite of many years of intense research. One o f its regulators is the cdk inhibitory molecule p21(WAF1)-a protein which i s expressed in situations of genotoxic stress. p21(WAF1) binds to the beta- subunit of CK2 and inhibits the activity of CK2. Using deletion mutants of CK2 beta as well as a peptide library consisting of 15-amino-acid-long pept ides derived from the polypeptide chain of CK2 beta we mapped the binding r egion for p21(WAF1) on the polypeptide chain of CK2 beta. We localized an a mino-terminal and a carboxy-terminal binding domain. Binding of p21(WAF1) t o both regions of the CK2 beta-subunit interferes with the phosphotransfera se activity of the CK2 holoenzyme. (C) 2000 Academic Press.