Premium
The PI3K‐Akt Pathway Regulates Calpain 6 Expression, Proliferation, and Apoptosis
Author(s) -
Zha Xiliang
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb142
Subject(s) - pi3k/akt/mtor pathway , protein kinase b , signal transduction , transcription factor , microbiology and biotechnology , promoter , ap 1 transcription factor , apoptosis , biology , transcription (linguistics) , cancer research , chemistry , gene expression , gene , genetics , linguistics , philosophy
Objective Calpain 6 Expression Regulated by the PI3K‐Akt Pathway and its mechanism. Results According to the data that CAPN6 was up‐regulated in the Akt transformed mouse embryonic fibroblast cells by cDNA chip, the mechanisms underlying elevated CAPN6 expression by PI3K‐Akt signaling pathway and its biological functions were studied. The results showed that CAPN6 was down‐regulated on transcriptional and post‐transcriptional levels by the PI3K inhibitor or Akt deletion. CAPN6 protein was stabilized by PI3K‐GSK‐3β pathway. Deleted CAPN6 promoters activity were assessed by dual‐luciferase reporter system, and the founding indicated that −93/+200 DNA fragment was the core promoter of it. Transcription factor binding sites in the CAPN6 promoter were mutated and the results showed that AP1, Oct‐1, and FoxD3 were the critical transcription factors in regulation of CAPN6 expression. In addition, CAPN6 promoted cancer cell proliferation and inhibited its apoptosis. Conclusion The finding demonstrates that CAPN6 is regulated by the PI3K‐Akt signaling pathway and provides evidence that it may be a therapeutic target of cancer.