Sec5 and Exo84 foster oncogenic ras-mediated tumorigenesis.

Published

Journal Article

The genes encoding the Ras family of small GTPases are mutated to yield constitutively active GTP-bound oncogenic proteins in one third of all human cancers. Oncogenic Ras binds to and activates a number of proteins that promote tumorigenic phenotypes, including the family of Ral guanine nucleotide exchange factors (RalGEF). Activated RalGEFs convert the Ral family of small GTPases, composed of RalA and RalB, from an inactive GDP-bound state to an active GTP-bound state. As both RalA and RalB have been implicated in a variety of tumorigenic phenotypes, we sought to determine which proteins downstream of Rals promote transformation and tumorigenesis. Here, we report that shRNA-mediated knockdown of the Ral effector proteins Sec5 and Exo84, but less so in the case of RalBP1, reduced oncogenic RalGEF-mediated transformation and oncogenic Ras-driven tumorigenic growth of human cells. These results suggest that Rals promote oncogenic Ras-mediated tumorigenesis through, at least in part, Sec5 and Exo84.

Full Text

Duke Authors

Cited Authors

  • Issaq, SH; Lim, K-H; Counter, CM

Published Date

  • February 2010

Published In

Volume / Issue

  • 8 / 2

Start / End Page

  • 223 - 231

PubMed ID

  • 20145037

Pubmed Central ID

  • 20145037

Electronic International Standard Serial Number (EISSN)

  • 1557-3125

Digital Object Identifier (DOI)

  • 10.1158/1541-7786.MCR-09-0189

Language

  • eng

Conference Location

  • United States