A novel cyclin associates with M015/CDK7 to form the CDK-activating kinase

Fisher, Robert P.; Morgan, David O.

doi:10.1016/0092-8674(94)90535-5

Cited by 655Cancer-related Molecular PathwaysMicrotubule and mitosis dynamicsProtein Kinase Regulation and GTPase Signaling

A novel cyclin associates with M015/CDK7 to form the CDK-activating kinase

Fisher, Robert P., Morgan, David O.·1994·Cell

DOI 10.1016/0092-8674(94)90535-5

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Abstract

Phosphorylation by the CDK-activating kinase (CAK) is a required step in the activation of cyclin-dependent kinases. We have purified CAK from mammalian cells; the enzyme comprises two major polypeptides of 42 and 37 kDa. Protein sequencing indicates that the 42 kDa subunit is the mammalian homolog of MO15, a protein kinase known to be a component of CAK in amphibians and echinoderms. Cloning of a cDNA encoding the 37 kDa subunit identifies it as a novel cyclin (cyclin H). We have reconstituted CAK in vitro with the MO15 catalytic subunit and cyclin H, demonstrating that MO15 is a cyclin-dependent kinase (CDK7). Like other CDKs, MO15/CDK7 contains a conserved threonine required for full activity; mutation of this residue severely reduces CAK activity. The CAK holoenzyme activates complexes of CDK2 and CDC2 with various cyclins and also phosphorylates CDK2, but not CDC2, in the absence of cyclin. Thus, CAK is a CDK-cyclin complex implicated in the control of multiple cell cycle transitions.

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All three microglial sub-populations showed upregulation of APOE, ATG16L2, BCL2, CCNH and GAS7; negative regulators of senescence GRB2 and NIBAN1 were downregulated with increasing β-amyloid.
“All three microglial sub-populations showed upregulation of APOE, ATG16L2 (an autophagy antagonist gene), BCL2 (encoding a negative regulator of apoptosis), the CDK7 regulator gene CCNH and GAS7 (the growth arrest-specific protein 7 gene). Genes for negative regulators of senescence such as GRB2 and NIBAN1 were downregulated with increasing β-amyloid [17, 21, 34, 55].”
From Characterisation of premature cell senescence in Alzheimer's disease using single nuclear transcriptomics (2024) · cites this paper as [21]

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Authors: Fisher, R. P., & Morgan, D. O.
Affiliations: University of California, San Francisco (US)
ORCID: Fisher, Robert P.
Morgan, David O.
Venue: Cell
Publisher: Elsevier BV
Published: 1994-08
Volume: 78
Issue: 4
Pages: 713-724
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/0092-8674(94)90535-5
OpenAlex: W2027376766
Cited by: 655
References: 35
Citations by year: 2026: 10 · 2025: 8 · 2024: 12 · 2023: 11 · 2022: 12 · 2021: 14 · 2020: 9 · 2019: 15 · 2018: 9 · 2017: 13 · 2016: 11 · 2015: 11 · 2014: 9 · 2013: 16 · 2012: 14
FWCI: 25.52
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Funders: Helen Hay Whitney Foundation
Topics: Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords: CDK-activating kinase, cyclin H, CDK7, cyclin-dependent kinases, CDK2, cdc2, CDK activation, threonine phosphorylation, cell cycle regulation, cDNA cloning
MeSH terms: Cyclin-Dependent Kinase-Activating Kinase, Amino Acid Sequence, Animals, Base Sequence, Cloning, Molecular, HeLa Cells, Humans, Models, Biological, Molecular Sequence Data, Phosphorylation, Recombinant Fusion Proteins, Substrate Specificity, Cyclins, Sequence Alignment, Protein Serine-Threonine Kinases, Sequence Homology, Amino Acid, Sequence Analysis, Sequence Analysis, DNA, DNA, Complementary, Cyclin-Dependent Kinases, Mice, Cyclin H

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A novel cyclin associates with M015/CDK7 to form the CDK-activating kinase

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