Negative regulation of Par-4 by oncogenic Ras is essential for cellular transformation

Shirley Guofang Qiu, Sumathi Krishnan, Nadia El-Guendy, Vivek M. Rangnekar

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


Oncogenic variants of the cellular Ras protein are often associated with different types of human cancers. However, the mechanisms by which oncogenic Ras induces transformation are not fully established. Expression of the transcriptional repressor Par-4 was down-regulated by oncogenic Ras via the Raf-MEK-ERK pathway. Restoration of Par-4 levels by abrogation of the Raf-MEK-ERK pathway with the MEK-inhibitor PD98059 or by ectopic Par-4, that acted to inhibit ERK expression and activation, was sufficient to suppress oncogenic Ras-induced transformation. These findings identify Par-4 as a novel target that has to be down-modulated by oncogenic Ras for successful transformation.

Original languageEnglish
Pages (from-to)7115-7123
Number of pages9
Issue number50
StatePublished - Nov 25 1999

Bibliographical note

Funding Information:
This work was supported by the NIH Grant R01 CA60872 (to VM Rangnekar).


  • ERK
  • Par-4
  • Pas
  • Transformation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research


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