SUMO-1 represses apoptosis signal-regulating kinase 1 activation through physical interaction and not through covalent modification.
This study examined whether small ubiquitin-related modifier-1 (SUMO-1) regulates apoptosis signal-regulating kinase 1 (ASK 1). ASK 1 interacted with SUMO-1 in vitro as well as in BOSC 23 cells. Endogenous ASK 1-SUMO-1 interaction was disrupted following H(2)O(2) signal. SUMO-1 overexpression suppressed the self-oligomerization, kinase activity and apoptotic potential of ASK 1, whereas SUMO-1 depletion potentiated such activities. SUMO-1(Delta C 6), a sumoylation-incompetent mutant lacking carboxy-terminal six amino acids, suppressed AS 1 activation, implying that the suppressive effect of SUMO-1 on ASK 1 is independent of sumoylation. ASK 1(3M), an ASK 1 mutant in which all three lysines in the psiKXE motif were substituted with alanines, still retained the kinase activity and activated the Jun amino-terminal kinase pathway. However, SUMO-1 failed to interact with ASK 1(3M) and to suppress ASK 1(3M) activation, indicating that the three lysines are important for regulation by SUMO-1. This study shows that SUMO-1 exerts a negative regulatory effect on ASK 1 activation through physical interaction and not through covalent modification.
Lee
Yun-Suk
YS
Research Center for Biomedicinal Resources, PaiChai University, 439-6 Doma 2-Dong, Seo-gu, Daejeon 302-735, Korea.
Jang
Moon-Sun
MS
Lee
Jong-Soo
JS
Choi
Eui-Ju
EJ
Kim
Eunhee
E
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D015536:Down-Regulation; D004789:Enzyme Activation; D047468:Immunoprecipitation; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism*; D051379:Mice; D010957:Plasmids / Q000235:genetics; D011499:Protein Processing, Post-Translational; D012097:Repressor Proteins; D025842:SUMO-1 Protein / Q000502:physiology*; D015398:Signal Transduction; D014162:Transfection
D012097:Repressor Proteins; D025842:SUMO-1 Protein; D048031:JNK Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5