Positive regulation of apoptosis signal-regulating kinase 1 by dual-specificity phosphatase 13A |
| |
Authors: | Jae Eun Park Byoung Chul Park Hyun-A Kim Mina Song Sung Goo Park Do Hee Lee Hyeoung-Joon Kim Hyung-Kyoon Choi Jong-Tae Kim Sayeon Cho |
| |
Affiliation: | (1) Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-806, Korea;(2) College of Pharmacy, Chung-Ang University, Seoul, 156-756, Korea;(3) Department of Biotechnology, College of Natural Sciences, Seoul Women’s University, Seoul, 139-774, Korea;(4) Genome Research Center for Hematopoietic Diseases, Chonnam National University Hospital, Hwasun-gun, Jeonnam, 519-809, Korea;(5) Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-806, Korea |
| |
Abstract: | Apoptosis signal-regulating kinase 1 (ASK1), a member of the MAP kinase kinase kinase, is activated by several death stimuli and is tightly regulated by several mechanisms such as interactions with regulatory proteins and post-translational modifications. Here, we report that dual-specificity phosphatase 13A (DUSP13A) functions as a novel regulator of ASK1. DUSP13A interacts with the N-terminal domain of ASK1 and induces ASK1-mediated apoptosis through the activation of caspase-3. DUSP13A enhances ASK1 kinase activity and thus its downstream factors. Small interfering RNA (siRNA) analyses show that knock-down of DUSP13A in human neuroblastoma SK-N-SH cells reduces ASK1 kinase activity. The phosphatase activity of DUSP13A is not required for the regulation of ASK1. This regulatory action of DSUP13 on ASK1 activity involves competition with Akt1, a negative regulator of ASK1, for binding to ASK1. Taken together, this study provides novel insights into the role of DUSP13A in the precise regulation of ASK1. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|