The HECTD3 E3 ubiquitin ligase suppresses cisplatin-induced apoptosis via stabilizing MALT1

Yi Li, Xi Chen, Zehua Wang, Dong Zhao, Hui Chen, Wenlin Chen, Zhongmei Zhou, Junran Zhang, Jing Zhang, Hongmin Li, Ceshi Chen

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Homologous to the E6-associated protein carboxyl terminus domain containing 3 (HECTD3) is an E3 ubiquitin ligase with unknown functions. Here, we show that HECTD3 confers cancer cell resistance to cisplatin. To understand the molecular mechanisms, we performed a yeast two-hybrid analysis and identified mucosa-associated lymphoid tissue 1 (MALT1) as an HECTD3-interacting protein. HECTD3 promotes MALT1 ubiquitination with nondegradative polyubiquitin chains by direct interacting with the MALT1 through its N-terminal destruction of cyclin domain. HECTD3 does not target MALT1 for degradation but stabilize it. HECTD3 depletion dramatically decreases the levels of MALT1 in MCF7 and HeLa cells treated with cisplatin, which is correlated to an increase in apoptosis. Knockdown of MALT1 likewise increases cisplatin-induced apoptosis in these cancer cells. However, HECTD3 overexpression leads to a decreased cisplatin-induced apoptosis, whereas overexpression of MALT1 partially rescues HECTD3 depletion-induced apoptosis. These findings suggest that HECTD3 promotes cell survival through stabilizing MALT1. Our data have important implications in cancer therapy by providing novel molecular targets.

Original languageEnglish (US)
Pages (from-to)39-48
Number of pages10
JournalNeoplasia (United States)
Volume15
Issue number1
DOIs
StatePublished - Jan 2013
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research

Fingerprint

Dive into the research topics of 'The HECTD3 E3 ubiquitin ligase suppresses cisplatin-induced apoptosis via stabilizing MALT1'. Together they form a unique fingerprint.

Cite this