Phosphorylation of caspase-7 by p21-activated protein kinase (PAK) 2 inhibits chemotherapeutic drug-induced apoptosis of breast cancer cell lines

Xiang Li, Weihong Wen, Kangdong Liu, Feng Zhu, Margarita L Malakhova, Cong Peng, Tingting Li, HONGGYUM KIM, Wei-Ya Ma, Yong Yeon Cho, Ann M. Bode, Ziming Dong, Zigang Dong

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

p21-activated kinase (PAK) 2, a member of the PAK family of serine/threonine protein kinases, plays an important role in physiological processes such as motility, survival, mitosis, and apoptosis. However, the role of PAK2 in resistance to chemotherapy is unclear. Here we report that PAK2 is highly expressed in human breast cancer cell lines and human breast invasive carcinoma tissue compared with a human non-tumorigenic mammary epithelial cell line and adjacent normal breast tissue, respectively. Interestingly, we found that PAK2 can bind with caspase-7 and phosphorylate caspase-7 at the Ser-30, Thr-173, and Ser-239 sites. Functionally, the phosphorylation of caspase-7 decreases its activity, thereby inhibiting cellular apoptosis. Our data indicate that highly expressed PAK2 mediates chemotherapeutic resistance in human breast invasive ductal carcinoma by negatively regulating caspase-7 activity.

Original languageEnglish (US)
Pages (from-to)22291-22299
Number of pages9
JournalJournal of Biological Chemistry
Volume286
Issue number25
DOIs
StatePublished - Jun 24 2011

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