Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals

Cell. 1994 Jul 15;78(1):59-66. doi: 10.1016/0092-8674(94)90572-x.

Abstract

We cloned p27Kip1, a cyclin-dependent kinase inhibitor implicated in G1 phase arrest by TGF beta and cell-cell contact. p27Kip1 associates with cyclin E-Cdk2 complexes in vivo and in vitro, prevents their activation, and inhibits previously activated complexes, and p27Kip1 overexpression obstructs cell entry into S phase. p27Kip1 potently inhibits Rb phosphorylation by cyclin E-Cdk2, cyclin A-Cdk2, and cyclin D2-Cdk4. p27Kip1 is highly conserved and broadly expressed in human tissues, and its mRNA levels are similar in proliferating and quiescent cells. p27Kip1 has a region of sequence similarity to p21Cip1/WAF1, the Cdk inhibitor whose transcription is stimulated by p53. A p27Kip1 peptide corresponding to this region retains Cdk inhibitory activity. We suggest that cell contact, TGF beta, and p53 all restrain cell proliferation through related Cdk inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CDC2-CDC28 Kinases*
  • Cell Cycle Proteins*
  • Cell Line
  • Cloning, Molecular
  • Contact Inhibition
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinases*
  • Cyclins / metabolism*
  • Fungal Proteins / genetics*
  • Fungal Proteins / isolation & purification
  • Fungal Proteins / metabolism
  • Fungal Proteins / pharmacology*
  • G1 Phase / drug effects*
  • Humans
  • Mice
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / isolation & purification
  • Microtubule-Associated Proteins / metabolism
  • Microtubule-Associated Proteins / pharmacology*
  • Mink
  • Molecular Sequence Data
  • Organ Specificity
  • Protein Kinase Inhibitors*
  • Protein Kinases / metabolism
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins*
  • RNA, Messenger / analysis
  • Sequence Alignment
  • Sequence Analysis
  • Transforming Growth Factor beta / pharmacology
  • Tumor Suppressor Proteins*

Substances

  • Cdkn1b protein, mouse
  • Cell Cycle Proteins
  • Cyclins
  • Fungal Proteins
  • Microtubule-Associated Proteins
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • CDC2-CDC28 Kinases
  • CDK2 protein, human
  • CDK4 protein, human
  • Cdk2 protein, mouse
  • Cdk4 protein, mouse
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases

Associated data

  • GENBANK/U09966
  • GENBANK/U09968
  • GENBANK/U10906