Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes

Ratna K. Vadlamudi, Rozita Bagheri-Yarmand, Zhibo Yang, Seetharaman Balasenthil, Diep Nguyen, Aysegul A. Sahin, Petra Den Hollander, Rakesh Kumar

Research output: Contribution to journalArticlepeer-review

148 Scopus citations

Abstract

We identified dynein light chain 1 (DLC1) as a physiologic substrate of p21-activated kinase 1 (Pak1). Pak1-DLC1 interaction plays an essential role in cell survival, which depends on Pak1's phosphorylation of DLC1 on Ser88. Pak1 associates with the complex of DLC1 and BimL, a proapoptotic BH3-only protein, and phosphorylates both proteins. Phosphorylation of BimL by Pak1 prevents it from interacting with and inactivation of Bcl-2, an antiapoptotic protein. Overexpression of DLC1 but not DLC1-Ser88Ala mutant promotes cancerous properties of breast cancer cells. DLC1 protein level is elevated in more than 90% of human breast tumors. The regulation of cell survival functions by Pak1-DLC1 interaction represents a novel mechanism by which a signaling kinase might regulate the cancerous phenotypes.

Original languageEnglish (US)
Pages (from-to)575-585
Number of pages11
JournalCancer Cell
Volume5
Issue number6
DOIs
StatePublished - Jun 2004

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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