ALTERNATIVE MECHANISMS OF CAK ASSEMBLY REQUIRE AN ASSEMBLY FACTOR OR AN ACTIVATING KINASE

We have cloned a mouse cDNA that encodes p36, a novel subunit of the C DK-activating kinase (CAK). p36 contains a C3HC4 zinc-binding domain o r RING finger and is associated both with a TFIIH-bound form of CAK an d with a free trimeric form. p36 promotes the assembly of CDK7 and cyc lin H in vitro, stabilizing the transient CDK7-cyclin H complex. Stabi lization and activation of CAK by p36 is independent of the phosphoryl ation state of T170, the conserved activating residue of CDK7. Assembl y of active CDK7-cyclin H dimers can also occur through an alternative p36-independent pathway that requires phosphorylation of T170 by a CA K-activating kinase, or CAKAK. Thus, CDK7-cyclin H complex formation c an be achieved by multiple mechanisms.