Positive regulation of apoptosis signal-regulating kinase 1 by dual-specificity phosphatase 13A.

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.

• 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
• Journal: Cellular and molecular life sciences : CMLS (Cell Mol Life Sci) Vol. 67 Issue 15 Pg. 2619-29 (Aug 2010) ISSN: 1420-9071 [Electronic] Switzerland
• PMID: 20358250 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Small Interfering
• Phosphotransferases
• Proto-Oncogene Proteins c-akt
• MAP Kinase Kinase Kinase 5
• MAP Kinase Kinase Kinases
• Dual-Specificity Phosphatases
• Caspase 3

Topics

• Apoptosis (drug effects, genetics, physiology)
• Caspase 3 (genetics, metabolism)
• Dual-Specificity Phosphatases
• Humans
• MAP Kinase Kinase Kinase 5 (genetics, metabolism)
• MAP Kinase Kinase Kinases (genetics, metabolism)
• Neuroblastoma (genetics)
• Phosphotransferases (genetics, metabolism)
• Protein Processing, Post-Translational (drug effects)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• RNA, Small Interfering (genetics, metabolism)
• Signal Transduction (drug effects, genetics, physiology)