Positive regulation of apoptosis signal-regulating kinase 1 by dual-specificity phosphatase 13A.
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.
Park
Jae Eun
JE
Medical Proteomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
Park
Byoung Chul
BC
Kim
Hyun-A
HA
Song
Mina
M
Park
Sung Goo
SG
Lee
Do Hee
DH
Kim
Hyeoung-Joon
HJ
Choi
Hyung-Kyoon
HK
Kim
Jong-Tae
JT
Cho
Sayeon
S
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*
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