Cab45S promotes cell proliferation through SERCA2b inhibition and Ca2+ signaling

被引：24

作者：

Chen, L. ^{[1
]}

Xu, S. ^{[1
]}

Xu, Y. ^{[1
]}

Lu, W. ^{[1
]}

Liu, L. ^{[1
]}

Yue, D. ^{[1
]}

Teng, J. ^{[1
]}

Chen, J. ^{[1
,2
]}

机构：

[1] Peking Univ, Coll Life Sci, State Key Lab Biomembrane & Membrane Bioengn, Key Lab Cell Proliferat & Differentiat,Minist Edu, Beijing 100871, Peoples R China

[2] Peking Univ, Ctr Quantitat Biol, Beijing 100871, Peoples R China

来源：

ONCOGENE | 2016年 / 35卷 / 01期

基金：

中国国家自然科学基金;

关键词：

INTESTINAL EPITHELIAL-CELLS; THERAPEUTIC TARGET; ER STRESS; STORE; STIM1; CANCER; CALCINEURIN; APOPTOSIS; FAMILY; TRPC1;

D O I：

10.1038/onc.2015.56

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Cytosolic Ca2+, closely related to endoplasmic reticulum (ER) Ca2+, plays a critical role in regulating cell proliferation and tumorigenesis. However, the role of ER lumen proteins in regulating cytosolic Ca2+ level remains poorly understood. Here, we find that the Cab45S, localizes in the ER lumen, inhibits sarco/ER Ca2+-ATPase 2b (SERCA2b) activity through its first EF-hand domain directly binding to the intra-lumenal loop 4 of SERCA2b, and reduces ER Ca2+. STIM1 activation, induced by the Cab45S-dependent drop in ER Ca2+, together with the upregulation of the plasma membrane Ca2+ channel TRPC1 ultimately increases extracellular Ca2+ influx. Furthermore, increased cytosolic Ca2+ level elicits Ca2+-NFAT signaling and promotes cell proliferation. Consistently, in cervical carcinoma patients, Cab45S is upregulated. Thus, our data reveal that the ability of Cab45S to inhibit SERCA2b activity is crucial for its role as a modulator of cell proliferation and tumor growth.

引用

页码：35 / 46

页数：12

共 59 条

[1] Stim1 and Orai1 Mediate CRAC Currents and Store-Operated Calcium Entry Important for Endothelial Cell Proliferation [J].