HCMV IE72 Control Over PML, the Human Breast Cancer Tumor Suppressor

Abstract

Our investigation into the relationships between the host growth and transformation suppressor, PML and HCMV kinase 1E72, has furthered our understanding of PML and its role in nuclear structure (POD) maintenance. PML/PODs are involved in cell cycle control, apoptosis, and oncogenesis. Therefore, we have used the viral kinase, 1E72 as a tool to decipher the mechanisms of POD assembly and PML suppressor function. We have accumulated much data to support our hypothesis: We demonstrate that 1E72 preferentially binds the SUMO-l modified, POD-associated PML and phosphorylates PML, thereby mediating PML de-sumoylation and contributing to POD distruption. We also provide evidence that 1E72 kinase activity regulates PML stability. We have narrowed the identification of the serine(s) involved in regulating PML stability to 9. It is our contention that the identification of these important regulatory phospho-amino acids will allow for the design of a PML based anti-cancer strategy.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2001
Accession Number
ADB273871

Entities

People

  • Mary L. Spengler

Organizations

  • Health Research, Incorporated

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Apoptosis
  • Biomedical And Dental Materials
  • Breast Cancer
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Identification
  • Immediate-Early Proteins
  • Infection
  • Macrophages
  • Neoplasms
  • Nuclear Structure
  • Peptides
  • Polymeric Films
  • Proteins
  • Viruses

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  • Molecular Biology and Genetics