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PMID:11447116

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Citation

Larochelle, S, Chen, J, Knights, R, Pandur, J, Morcillo, P, Erdjument-Bromage, H, Tempst, P, Suter, B and Fisher, RP (2001) T-loop phosphorylation stabilizes the CDK7-cyclin H-MAT1 complex in vivo and regulates its CTD kinase activity. EMBO J. 20:3749-59

Abstract

Cyclin-dependent kinase (CDK)7-cyclin H, the CDK-activating kinase (CAK) and TFIIH-associated kinase in metazoans can be activated in vitro through T-loop phosphorylation or binding to the RING finger protein MAT1. Although the two mechanisms can operate independently, we show that in a physiological setting, MAT1 binding and T-loop phosphorylation cooperate to stabilize the CAK complex of Drosophila. CDK7 forms a stable complex with cyclin H and MAT1 in vivo only when phosphorylated on either one of two residues (Ser164 or Thr170) in its T-loop. Mutation of both phosphorylation sites causes temperature-dependent dissociation of CDK7 complexes and lethality. Furthermore, phosphorylation of Thr170 greatly stimulates the activity of the CDK7- cyclin H-MAT1 complex towards the C-terminal domain of RNA polymerase II without significantly affecting activity towards CDK2. Remarkably, the substrate-specific increase in activity caused by T-loop phosphorylation is due entirely to accelerated enzyme turnover. Thus phosphorylation on Thr170 could provide a mechanism to augment CTD phosphorylation by TFIIH-associated CDK7, and thereby regulate transcription.

Links

PubMed PMC125544 Online version:10.1093/emboj/20.14.3749

Keywords

Amino Acid Sequence; Animals; Biopolymers; Cyclin H; Cyclin-Dependent Kinases; Cyclins/antagonists & inhibitors; Cyclins/metabolism; Drosophila; Drosophila Proteins; Kinetics; Molecular Sequence Data; Phosphorylation; Protein Kinases/metabolism; Protein-Serine-Threonine Kinases/antagonists & inhibitors; Protein-Serine-Threonine Kinases/metabolism; Substrate Specificity

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:O17144

involved_in

GO:0000079: regulation of cyclin-dependent protein serine/threonine kinase activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:O17144

part_of

GO:0032806: carboxy-terminal domain protein kinase complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:O76513

involved_in

GO:0000079: regulation of cyclin-dependent protein serine/threonine kinase activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:O76513

part_of

GO:0032806: carboxy-terminal domain protein kinase complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:Q24216

enables

GO:0008353: RNA polymerase II CTD heptapeptide repeat kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:Q24216

enables

GO:0004693: cyclin-dependent protein serine/threonine kinase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:Q24216

part_of

GO:0032806: carboxy-terminal domain protein kinase complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:Q7KPG8

involved_in

GO:0000079: regulation of cyclin-dependent protein serine/threonine kinase activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:Q7KPG8

enables

GO:0043539: protein serine/threonine kinase activator activity

ECO:0000304: author statement supported by traceable reference used in manual assertion

F

Seeded From UniProt

complete

DROME:Q7KPG8

part_of

GO:0032806: carboxy-terminal domain protein kinase complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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