title: Alternative mechanisms of CAK assembly require an assembly factor or an activating kinase.
abstract: We have cloned a mouse cDNA that encodes p36, a novel subunit of the CDK-activating kinase (CAK). p36 contains a C3HC4 zinc-binding domain or RING factor and is associated both with a TFIIH-bound form of CAK and with a free trimeric form. p36 promotes the assembly of CDK7 and cyclin H in vitro, stabilizing the transient CDK7-cyclin H complex. Stabilization and activation of CAK by p36 is independent of the phosphorylation state of T170, the conserved activating residue of CDK7. Assembly of active CDK7-cyclin H dimers can also occur through an alternative p36-independent pathway that requires phosphorylation of T170 by a CAK-activating kinase, or CAKAK. Thus, CDK7-cyclin H complex formation can be achieved by multiple mechanisms.
authors.affiliation: Department of Physiology, University of California, San Francisco 94143-0444, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Fisher
authors.forename: P
authors.initials: P
authors.lastname: Jin
authors.forename: H M
authors.initials: HM
authors.lastname: Chamberlin
authors.forename: D O
authors.initials: DO
authors.lastname: Morgan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D056748:Cyclin H; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics*; D005246:Feedback; D051379:Mice; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016415:Sequence Alignment; D000095043:Cyclin-Dependent Kinase-Activating Kinase
chemical_list: D056748:Cyclin H; D018844:Cyclin-Dependent Kinases; D016213:Cyclins; D018076:DNA, Complementary; D017346:Protein Serine-Threonine Kinases; D000095043:Cyclin-Dependent Kinase-Activating Kinase; C534752:Ccnh protein, mouse; C090586:Cdk7 protein, mouse