Distinctive roles of PHAP proteins and prothymosin-alpha in a death regulatory pathway |
| |
| Authors: | Jiang Xuejun Kim Hyun-Eui Shu Hongjun Zhao Yingming Zhang Haichao Kofron James Donnelly Jennifer Burns Dave Ng Shi-Chung Rosenberg Saul Wang Xiaodong |
| |
| Institution: | Howard Hughes Medical Institute, Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. |
| |
| Abstract: | A small molecule, alpha-(trichloromethyl)-4-pyridineethanol (PETCM), was identified by high-throughput screening as an activator of caspase-3 in extracts of a panel of cancer cells. PETCM was used in combination with biochemical fractionation to identify a pathway that regulates mitochondria-initiated caspase activation. This pathway consists of tumor suppressor putative HLA-DR-associated proteins (PHAP) and oncoprotein prothymosin-alpha (ProT). PHAP proteins promoted caspase-9 activation after apoptosome formation, whereas ProT negatively regulated caspase-9 activation by inhibiting apoptosome formation. PETCM relieved ProT inhibition and allowed apoptosome formation at a physiological concentration of deoxyadenosine triphosphate. Elimination of ProT expression by RNA interference sensitized cells to ultraviolet irradiation-induced apoptosis and negated the requirement of PETCM for caspase activation. Thus, this chemical-biological combinatory approach has revealed the regulatory roles of oncoprotein ProT and tumor suppressor PHAP in apoptosis. |
| |
| Keywords: | |
| 本文献已被 PubMed 等数据库收录！ |
|
