Open AccessiASPP suppresses Gp78-mediated TMCO1 degradation to maintain Ca 2+ homeostasis and control tumor growth and drug resistance
Author(s) -
S. Zheng,
Zhao Dong,
Guixue Hou,
Song Zhao,
Wenxin Zhang,
Xingwen Wang,
Li Li,
Liang Lin,
Tie-Shan Tang,
Ying Hu
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2111380119
Subject(s) - endoplasmic reticulum , homeostasis , microbiology and biotechnology , ubiquitin ligase , biology , apoptosis , cell growth , unfolded protein response , programmed cell death , oncogene , downregulation and upregulation , ubiquitin , cell cycle , biochemistry , gene
Significance Accumulating preclinical and clinical evidence has supported a central role for alterations in Ca2+ homeostasis in the development of cancer. TMCO1 protein is an identified Ca2+ -channel protein, while its roles in cancer remain obscure. Here, we found that TMCO1 is increased in colon cancer tissues. In addition, it is a substrate of E3 ligase Gp78. Enhanced oncogene iASPP stabilizes TMCO1 by competitively binding with Gp78. Inhibition of iASPP-TMCO1 sensitizes cancer cells’ response to Ca2+ -induced apoptosis. This study has improved our fundamental understanding of the Ca2+ homeostasis in cancer cells. iASPP-TMCO1 axis may present a promising therapeutic target that can combine the conventional drugs to reinforce Ca2+ -dependent apoptosis.