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 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.
Fisher
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RP
Department of Physiology, University of California, San Francisco 94143-0444, USA.
Jin
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Chamberlin
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Morgan
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DO
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
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