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 journalArticle

144 Citations (Scopus)

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
Externally publishedYes

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p21-Activated Kinases
Dyneins
Phenotype
Cell Survival
Proteins
Phosphorylation
Breast Neoplasms
Phosphotransferases

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Vadlamudi, R. K., Bagheri-Yarmand, R., Yang, Z., Balasenthil, S., Nguyen, D., Sahin, A. A., ... Kumar, R. (2004). Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes. Cancer Cell, 5(6), 575-585. https://doi.org/10.1016/j.ccr.2004.05.022

Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes. / Vadlamudi, Ratna K; Bagheri-Yarmand, Rozita; Yang, Zhibo; Balasenthil, Seetharaman; Nguyen, Diep; Sahin, Aysegul A.; Den Hollander, Petra; Kumar, Rakesh.

In: Cancer Cell, Vol. 5, No. 6, 06.2004, p. 575-585.

Research output: Contribution to journalArticle

Vadlamudi, RK, Bagheri-Yarmand, R, Yang, Z, Balasenthil, S, Nguyen, D, Sahin, AA, Den Hollander, P & Kumar, R 2004, 'Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes', Cancer Cell, vol. 5, no. 6, pp. 575-585. https://doi.org/10.1016/j.ccr.2004.05.022
Vadlamudi, Ratna K ; Bagheri-Yarmand, Rozita ; Yang, Zhibo ; Balasenthil, Seetharaman ; Nguyen, Diep ; Sahin, Aysegul A. ; Den Hollander, Petra ; Kumar, Rakesh. / Dynein light chain 1, a p21-activated kinase 1-interacting substrate, promotes cancerous phenotypes. In: Cancer Cell. 2004 ; Vol. 5, No. 6. pp. 575-585.
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