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UV irradiation resistance‐associated gene suppresses apoptosis by interfering with BAX activation
Author(s) -
Yin Xiaocheng,
Cao Lizhi,
Kang Rui,
Yang Minghua,
Wang Zhuo,
Peng Yanhui,
Tan Yanfang,
Liu Liying,
Xie Min,
Zhao Yiming,
Livesey Kristen M,
Tang Daolin
Publication year - 2011
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2011.79
Subject(s) - autophagy , apoptosis , microbiology and biotechnology , mitochondrion , cytochrome c , biology , rna interference , programmed cell death , suppressor , small interfering rna , transfection , chemistry , cancer research , gene , rna , biochemistry
Ultraviolet irradiation resistance‐associated gene ( UVRAG ) is a well‐known regulator of autophagy by promoting autophagosome formation and maturation. However, little is known about the non‐autophagic functions of UVRAG. Here, we present evidence that UVRAG functions as an unusual BCL2‐associated X protein (Bax) suppressor to regulate apoptosis. Chemotherapy and radiation induces UVRAG expression and subsequently upregulates autophagy and apoptosis in tumour cells. Depletion of UVRAG expression by RNA interference renders tumour cells more sensitive to chemotherapy‐ and radiation‐induced apoptosis in vitro and in vivo . Moreover, UVRAG interacts with Bax, which inhibits apoptotic stimuli‐induced mitochondrial translocation of Bax, reduction of mitochondrial membrane potential, cytochrome c release and activation of caspase‐9 and ‐3. Our findings show that UVRAG has an essential role in the intrinsic mitochondrial pathway of apoptosis by regulating the localization of Bax. This pathway represents a target for clinical intervention against tumours.