Use P27KIP1 Degradation for Breast Cancer Diagnosis and Therapy

Abstract

P27 IS A CDK inhibitor that controls the Gl/S transition. Low or absent expression of p27 has been observed in many malignant tumors including breast cancer. SCF(SKP2) is a ubiquitin E3 ligase that interacts and targets p27 for ubiquitin-dependent proteolysis. One aim of the proposal is to determine whether there is an inverse relationship between SCF(SKP2) and p27 in breast cancer and the experiments are in progress. Another aim is to determine the domain on SKP2 that binds to p27. We have determined the carboxy-terminal region of SKP2 is required for binds to phosphorylated p27. The critical aim is to determine whether inhibition of SCF(SKP2) in breast cancer cells causes cell cycle arrest. Our studies suggest that inhibition of SCF(SKP2) in breast cancer and other cancer cells causes accumulation of p27 and Gi cell cycle block. Thus SCF(SKP2) may be used as a target for breast cancer therapy.

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Document Details

Document Type
Technical Report
Publication Date
Jul 01, 2002
Accession Number
ADA412764

Entities

People

  • Hui Zhang

Organizations

  • Yale University

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Biomedical Research
  • Breast Cancer
  • Cancer
  • Carrier Proteins
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Culture Techniques
  • Developmental Biology
  • Genetic Structures
  • Genetics
  • Inhibition
  • Inhibitors
  • Neoplasms
  • Proteins
  • Tumor Cell Line

Fields of Study

  • Chemistry
  • Medicine

Readers

  • Marksmanship and Weaponry.
  • Molecular Biology and Genetics