title: 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.affiliation: Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
authors.forename: Jae Eun
authors.initials: JE
authors.lastname: Park
authors.forename: Byoung Chul
authors.initials: BC
authors.lastname: Park
authors.forename: Hyun-A
authors.initials: HA
authors.lastname: Kim
authors.forename: Mina
authors.initials: M
authors.lastname: Song
authors.forename: Sung Goo
authors.initials: SG
authors.lastname: Park
authors.forename: Do Hee
authors.initials: DH
authors.lastname: Lee
authors.forename: Hyeoung-Joon
authors.initials: HJ
authors.lastname: Kim
authors.forename: Hyung-Kyoon
authors.initials: HK
authors.lastname: Choi
authors.forename: Jong-Tae
authors.initials: JT
authors.lastname: Kim
authors.forename: Sayeon
authors.initials: S
authors.lastname: Cho
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D054637:Dual-Specificity Phosphatases; D006801:Humans; D048848:MAP Kinase Kinase Kinase 5 / Q000235:genetics / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D009447:Neuroblastoma / Q000235:genetics; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
chemical_list: D034741:RNA, Small Interfering; D010770:Phosphotransferases; D051057:Proto-Oncogene Proteins c-akt; D048848:MAP Kinase Kinase Kinase 5; D020930:MAP Kinase Kinase Kinases; D054637:Dual-Specificity Phosphatases; D053148:Caspase 3