iASPP suppresses Gp78-mediated TMCO1 degradation to maintain Ca 2+ homeostasis and control tumor growth and drug resistance | Zendy

Shanliang Zheng | Zendy; Dong Zhao | Zendy; Guixue Hou | Zendy; Song Zhao | Zendy; Wenxin Zhang | Zendy; Xingwen Wang | Zendy; Li Li | Zendy; Liang Lin | Zendy; Tie-Shan Tang | Zendy; Ying Hu | Zendy

Open Access

iASPP suppresses Gp78-mediated TMCO1 degradation to maintain Ca ²⁺ homeostasis and control tumor growth and drug resistance

Author(s) -

Shanliang Zheng,

Dong Zhao,

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

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) - homeostasis , apoptosis , ubiquitin ligase , oncogene , cancer , microbiology and biotechnology , biology , downregulation and upregulation , cancer cell , cancer research , ubiquitin , chemistry , biochemistry , cell cycle , gene , genetics

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.

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