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PMID: 8741839 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Isolation and characterization of p19INK4d, a p16-related inhibitor specific to CDK6 and CDK4.

Molecular biology of the cell ·Vol. 7 ·No. 1 ·1996-01-00 ·Pages 57-70

Guan KL, Jenkins CW, Li Y, O'Keefe CL, Noh S, Wu X, Zariwala M, Matera AG, Xiong Y

Abstract

Cyclin-dependent kinases 4 and 6 are complexed with many small cellular proteins in vivo. We have isolated cDNA sequences, INK4d, encoding a 19-kDa protein that is associated with CDK6 in several hematopoietic cell lines. p19 shares equal similarity and a common ancestor with other identified inhibitors of the p16/INK4 family. p19 interacts with and inhibits the activity of both CDK4 and CDK6 and exhibits no detectable interaction with the other known CDKs. p19 protein is present in both cell nuclei and cytoplasm. The p19 gene has been mapped to chromosome 19p13.2, and the level of its mRNA expression varies widely between different tissues. In contrast to p21 and p27 whose interaction with CDK subunits is dependent on or stimulated by the cyclin subunit, the interaction of p19 and p18 with CDK6 is hindered by the cyclin protein. Binary cyclin D1-p18/p19 or cyclin D1-CDK6 complexes are highly stable and cannot be dissociated by excess amounts of cyclin D1 or p19/p18 proteins, suggesting that p16 inhibitors and D cyclins may interact with CDKs 4 and 6 in a competing or potentially mutually exclusive manner.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Carrier Proteins/genetics,isolation & purification,metabolism Cell Cycle Proteins Cell Line Chromosome Mapping Cloning, Molecular Cyclin-Dependent Kinase Inhibitor p16 Cyclin-Dependent Kinase Inhibitor p19 Cyclin-Dependent Kinases/antagonists & inhibitors,metabolism Enzyme Inhibitors/isolation & purification Gene Expression Regulation Humans Immunohistochemistry Molecular Sequence Data Organ Specificity Protein Binding RNA, Messenger/biosynthesis Rabbits
Chemicals
CDKN2D protein, human Carrier Proteins Cell Cycle Proteins Cyclin-Dependent Kinase Inhibitor p16 Cyclin-Dependent Kinase Inhibitor p19 Enzyme Inhibitors RNA, Messenger Cyclin-Dependent Kinases
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Guan K L
Department of Biological Chemistry, University of Michigan, Ann Arbor 48109-0606, USA.
Jenkins C W
Li Y
O'Keefe C L
Noh S
Wu X
Zariwala M
Matera A G
Xiong Y
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40 references, click to expand
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.7.1.57
Published
1996-01-00
Pages
57-70
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC278612
Subset
IM
Grants
NCI NIH HHS · CA-65572 · United States
NIGMS NIH HHS · GM-51586 · United States
Databases
GENBANK
U40343
External Links
PubMed source DOI: 10.1091/mbc.7.1.57 PMC Full Text View journal details
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