Stabilization of the survival motor neuron protein by ASK1

Jeong Eun Kwon; Eun Kyung Kim; Eui Ju Choi

doi:10.1016/j.febslet.2011.04.011

Stabilization of the survival motor neuron protein by ASK1

Jeong Eun Kwon, Eun Kyung Kim, Eui Ju Choi

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

Abstract

The survival motor neuron (SMN) is a spliceosomal snRNP-interacting protein that was initially identified as a defective molecule in spinal muscular atrophy (SMA). The disease severity of SMA is determined by SMN protein level. Here, we show that apoptosis signal-regulating kinase 1 (ASK1) stabilizes SMN protein by inhibiting SMN poly-ubiquitination, and that the kinase activity of ASK1 is less important than its ability to bind to SMN. Furthermore, depletion of ASK1 by RNA interference revealed that ASK1 modulates neurite outgrowth by regulating SMN protein level in NSC34 motor neuron-like cells. Collectively, our results suggest that ASK1 acts as a novel binding partner of SMN and controls the steady-state level of SMN through complex formation with SMN in neurite outgrowth. Structured summary of protein interactions: ASK1 physically interacts with SMN1 by anti tag coimmunoprecipitation (View interaction) SMN1 physically interacts with ASK1 by anti tag coimmunoprecipitation (View interaction) ASK1 physically interacts with SMN1 by anti bait coimmunoprecipitation (View interaction) ASK1 physically interacts with SMNdelta7 by two hybrid (View interaction).

Original language	English
Pages (from-to)	1287-1292
Number of pages	6
Journal	FEBS Letters
Volume	585
Issue number	9
DOIs	https://doi.org/10.1016/j.febslet.2011.04.011
Publication status	Published - 2011 May 6

Bibliographical note

Funding Information:
We thank H. Ichijo (University of Tokyo, Tokyo, Japan) for providing ASK1 cDNA. This work was supported by a Korea University Grant and by the National Research Foundation of Korea (NRF) grants ( 2006-0093855 , 20090080985 and 2009-0001197 ), by the Original Technology Research Program for Brain Science ( 20090081488 ) through NRF (E.-J.C.), by a NRF grant ( 2009-0067112 ) (E.K.K.), and by a NRF grant ( 351-2009-1-C00047 ) (J.E.K.) funded by the Korea government (the Ministry of Education and Human Resources Development, MEST). J.E.K. was supported by the Brain Korea 21 project of the Korea government (MEST).

Keywords

Apoptosis signal-regulating kinase 1 (ASK1)
Spinal muscular atrophy (SMA)
Survival motor neuron (SMN)
Ubiquitination

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/j.febslet.2011.04.011

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title = "Stabilization of the survival motor neuron protein by ASK1",

abstract = "The survival motor neuron (SMN) is a spliceosomal snRNP-interacting protein that was initially identified as a defective molecule in spinal muscular atrophy (SMA). The disease severity of SMA is determined by SMN protein level. Here, we show that apoptosis signal-regulating kinase 1 (ASK1) stabilizes SMN protein by inhibiting SMN poly-ubiquitination, and that the kinase activity of ASK1 is less important than its ability to bind to SMN. Furthermore, depletion of ASK1 by RNA interference revealed that ASK1 modulates neurite outgrowth by regulating SMN protein level in NSC34 motor neuron-like cells. Collectively, our results suggest that ASK1 acts as a novel binding partner of SMN and controls the steady-state level of SMN through complex formation with SMN in neurite outgrowth. Structured summary of protein interactions: ASK1 physically interacts with SMN1 by anti tag coimmunoprecipitation (View interaction) SMN1 physically interacts with ASK1 by anti tag coimmunoprecipitation (View interaction) ASK1 physically interacts with SMN1 by anti bait coimmunoprecipitation (View interaction) ASK1 physically interacts with SMNdelta7 by two hybrid (View interaction).",

keywords = "Apoptosis signal-regulating kinase 1 (ASK1), Spinal muscular atrophy (SMA), Survival motor neuron (SMN), Ubiquitination",

author = "Kwon, {Jeong Eun} and Kim, {Eun Kyung} and Choi, {Eui Ju}",

note = "Funding Information: We thank H. Ichijo (University of Tokyo, Tokyo, Japan) for providing ASK1 cDNA. This work was supported by a Korea University Grant and by the National Research Foundation of Korea (NRF) grants ( 2006-0093855 , 20090080985 and 2009-0001197 ), by the Original Technology Research Program for Brain Science ( 20090081488 ) through NRF (E.-J.C.), by a NRF grant ( 2009-0067112 ) (E.K.K.), and by a NRF grant ( 351-2009-1-C00047 ) (J.E.K.) funded by the Korea government (the Ministry of Education and Human Resources Development, MEST). J.E.K. was supported by the Brain Korea 21 project of the Korea government (MEST).",

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Stabilization of the survival motor neuron protein by ASK1

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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