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CDK7/cyclin H complex, CDK-activating kinase (CAK) or p34cdc2 activating kinase

Function: - CAK is involved in controlling multiple cell cycle transitions phosphorylating many CDK/cyclin complexes - activation of CAK occurs through phosphorylation of Ser170 & Thr176 (presumably on CDK7) by another serine/threonine kinase - CAK activates the cyclin-associated kinases CDC2/CDK1, CDK2, CDK4 & CDK6 by threonine phosphorylation - CAK is a component of TFIIH & in this form phosphorylates the CTD of RNA polymerase 2 L' subunit [3]; this allows escape from the promoter & elongation of the transcripts - most CAK though is found separate from TFIIH - cyclin H/cdk7 complex preferentially phosphorylates cdk2 over RNA polymerase 2 CTD, however CAK & TFIIH show the opposite preference - TFIIH (not CAK) can also phosphorylate TFIIE & TFIIF [4] - kinase activity of CAK towards CDK's appears to be regulated largely by cyclin binding - CAK phosphorylates p34cdc2 on Thr161 Structure: - mammalian CAK appears to contain a 3rd subunit [2]

Interactions

molecular events

General

CDK/cyclin complex serine/threonine kinase

Properties

STATE: active state MOTIF: S/T phosphorylation site kinase domain MOTIF: ATP-binding site NAME: ATP-binding site SUBUNITS: cyclin-dependent kinase-7 (CDK7) STATE: active state MOTIF: kinase domain SITE: 12-295 MOTIF: ATP-binding site NAME: ATP-binding site SITE: 18-26 ATP-binding site NAME: ATP-binding site SITE: 41-41 aspartate residue {D137} Ser phosphorylation site {S164} Thr phosphorylation site {T170} binding site EFFECTOR-BOUND: cyclin H BOUND-VIA: cyclin box cyclin H MOTIF: Ser phosphorylation site {S5} cyclin box EFFECTOR-BOUND: cyclin-dependent kinase-7 (CDK7) BOUND-VIA: binding site Ser phosphorylation site {S304} glutamate-rich region {310-313} MOTIF: glutamate residue (SEVERAL) Thr phosphorylation site {T315} CDK-activating kinase assembly factor MAT1 MOTIF: acetylation site SITE: N-TERMINUS EFFECTOR-BOUND: acetyl RING-finger {6-50} EFFECTOR-BOUND: Zn+2 FOR-BINDING-OF: DNA motif Thr phosphorylation site {T51} UIM {142-161} Ser phosphorylation site {S205} Ser phosphorylation site {S279}

References

  1. Solomon MJ. The function(s) of CAK, the p34cdc2-activating kinase. Trends Biochem Sci. 1994 Nov;19(11):496-500. PMID: 7855894
  2. Morgan DO. Principles of CDK regulation. Nature. 1995 Mar 9;374(6518):131-4. Review. PMID: 7877684 (review CDK regulation)
  3. Shiekhattar R, Mermelstein F, Fisher RP, Drapkin R, Dynlacht B, Wessling HC, Morgan DO, Reinberg D. Cdk-activating kinase complex is a component of human transcription factor TFIIH. Nature. 1995 Mar 16;374(6519):283-7. PMID: 7533895 (presence in TFIIH)
  4. Dynlacht BD. Regulation of transcription by proteins that control the cell cycle. Nature. 1997 Sep 11;389(6647):149-52. Review. PMID: 9296491
  5. UniProt :accession P51946

Component-of

transcription factor IIH (TFIIH) or BTF2

Components

CDK-activating kinase assembly factor MAT1; RING finger protein MAT1; menage a trois; CDK7/cyclin-H assembly factor; p36; p35; cyclin-G1-interacting protein; RING finger protein 66 (MNAT1, CAP35, MAT1, RNF66) cyclin H (MO15-associated protein, CCNH) cyclin-dependent kinase-7 (CDK7) or p40M015