CFTR interacts with Hsp90 and regulates the phosphorylation of AKT and ERK1/2 in colorectal cancer cells

Liu, Kaisheng1,2; Jin, Hongtao1; Guo, Yaomin1; Liu, Ying1; Wan, Yong1; Zhao, Pan1; Zhou, Zhifan1; Wang, Jianhong1; Wang, Maolin3; Zou, Chang1; Wu, Weiqing1; Cheng, Zhiqiang1; Dai, Yong1

2019-06

10.1002/2211-5463.12641

FEBS Open Bio   影响因子和分区

2211-5463

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CF cells and tissues exhibit various mitochondrial abnormalities. However, the underlying molecular mechanisms remain elusive. Here, we examined the mechanisms through which CFTR regulates Bcl-2 family proteins, which in turn regulate permeabilization of the mitochondrial outer membrane. Notably, inhibition of CFTR activated Bax and Bad, but inhibited Bcl-2. Moreover, degradation of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and AKT increased significantly in CFTR-knockdown cells. Dysfunction of CFTR decreased heat-shock protein 90 (Hsp90) mRNA levels, and CFTR was found to interact with Hsp90. Inhibition of Hsp90 by SNX-2112 induced the degradation of phosphorylated AKT and ERK1/2 in Caco2 and HRT18 cells. These findings may help provide insights into the physiological role of CFTR in CF-related diseases.

AKT cystic fibrosis transmembrane conductance regulator extracellular signal-regulated kinase 1 2 heat-shock protein 90 mitochondria

SCI

英语

第一 ; 通讯

National Natural Science Foundation of China[81802749]

Biochemistry & Molecular Biology

Biochemistry & Molecular Biology

WOS:000480394000005

WILEY

Web of Science

1.Jinan Univ, Clin Med Coll 2, Southern Univ Sci & Technol, Affiliated Hosp 1,Shenzhen Peoples Hosp, Shenzhen, Peoples R China
2.Chinese Univ Hong Kong, Sch Biomed Sci, Fac Med, Hong Kong, Peoples R China
3.Shenzhen Univ, Hlth Sci Ctr, Sch Med, Shenzhen, Peoples R China

Liu, Kaisheng,Jin, Hongtao,Guo, Yaomin,et al. CFTR interacts with Hsp90 and regulates the phosphorylation of AKT and ERK1/2 in colorectal cancer cells[J]. FEBS Open Bio,2019,9(6):1119-1127.

Liu, Kaisheng.,Jin, Hongtao.,Guo, Yaomin.,Liu, Ying.,Wan, Yong.,...&Dai, Yong.(2019).CFTR interacts with Hsp90 and regulates the phosphorylation of AKT and ERK1/2 in colorectal cancer cells.FEBS Open Bio,9(6),1119-1127.

Liu, Kaisheng,et al."CFTR interacts with Hsp90 and regulates the phosphorylation of AKT and ERK1/2 in colorectal cancer cells".FEBS Open Bio 9.6(2019):1119-1127.