The PI3K-Akt pathway regulates calpain 6 expression, proliferation, and apoptosis

Yonglei Liu, Chuanzhong Mei, Lidong Sun, Xin Li, Mingzhu Liu, Liying Wang, Zengxia Li, Peng Yin, Chao Zhao, Yinghong Shi, Shuangjian Qiu, Jia Fan, Xiliang Zha
Cellular Signalling 2011, 23 (5): 827-36
The calpains are a family of cysteine proteases involved in some biological processes whose activities are highly dependent on Ca(2+). Calpain 6 (CAPN6), one member of the family, is unique in that it lacks the active-site cysteine residues for protease activity. 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. 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.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Available on the App Store

Available on the Play Store
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"