BRCA1 transactivates the cyclin-dependent kinase inhibitor p27(Kip1)

Oncogene. 2002 May 9;21(20):3199-206. doi: 10.1038/sj.onc.1205461.

Abstract

The p27(Kip1) is a member of the universal cyclin-dependent kinase inhibitor family. Previously, immunochemical analysis of a series of breast cancer cell lines demonstrated a correlation between the expression of p27(Kip1) and the breast cancer susceptibility gene BRCA1. BRCA1 has a number of activities including DNA repair, growth inhibition and as a transcription factor. Here we demonstrate that BRCA1 transactivates expression of p27(Kip1). This transactivation is dependent on the presence of a functional C-terminal transactivation domain. Promoter-deletion analysis identified the presence of a putative BRCA1-responsive element located at position -615 to -511 of the p27(Kip1) promoter. These results suggest that the transcriptional regulation of p27(Kip1) by BRCA1 may be a mechanism for BRCA1- induced growth inhibition.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / pathology
  • Animals
  • BRCA1 Protein / chemistry
  • BRCA1 Protein / physiology*
  • Breast Neoplasms / pathology
  • COS Cells / metabolism
  • Carcinoma, Ductal, Breast / pathology
  • Cell Cycle
  • Cell Cycle Proteins / biosynthesis
  • Cell Cycle Proteins / genetics*
  • Chlorocebus aethiops
  • Colonic Neoplasms / pathology
  • Cyclin-Dependent Kinase Inhibitor p27
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, BRCA1
  • Genes, Reporter
  • Humans
  • Mice
  • Neoplasm Proteins / metabolism
  • Promoter Regions, Genetic
  • Protein Structure, Tertiary
  • Sequence Deletion
  • Transcriptional Activation*
  • Transfection
  • Tumor Cells, Cultured / metabolism
  • Tumor Suppressor Proteins / biosynthesis
  • Tumor Suppressor Proteins / genetics*

Substances

  • BRCA1 Protein
  • Cdkn1b protein, mouse
  • Cell Cycle Proteins
  • Neoplasm Proteins
  • Tumor Suppressor Proteins
  • Cyclin-Dependent Kinase Inhibitor p27