GW112, a novel antiapoptotic protein that promotes tumor growth.
GW112 is a novel gene that has little homology to other known genes. It is overexpressed in a number of human tumor types, especially in those of the digestive system. We show here that GW112 is associated with GRIM-19, a protein known to be involved in regulating cellular apoptosis. Functionally, GW112 could significantly attenuate the ability of GRIM19 to mediate retinoic acid-IFN-beta-mediated cellular apoptosis and apoptosis-related gene expression. In addition, GW112 demonstrated strong antiapoptotic effects in tumor cells treated with other stress exposures such as hydrogen peroxide. Finally, forced overexpression of GW112 in murine prostate tumor cells led to more rapid tumor formation in a syngeneic host. Taken together, our data suggest that GW112 is an important regulator of cell death that plays important roles in tumor cell survival and tumor growth.
Zhang
Xiuwu
X
Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Huang
Qian
Q
Yang
Zhonghui
Z
Li
Yongping
Y
Li
Chuan-Yuan
CY
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D001798:Blood Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; D001798:Blood Proteins; C454127:OLFM4 protein, human; D016179:Granulocyte Colony-Stimulating Factor; D014212:Tretinoin; D016899:Interferon-beta; D006861:Hydrogen Peroxide; D009247:NADH, NADPH Oxidoreductases; C439057:NDUFA13 protein, human