Stabilization of the survival motor neuron protein by ASK1

Jeong Eun Kwon, Eun Kyung Kim, Eui Ju Choi

Research output: Contribution to journalArticle

10 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 languageEnglish
Pages (from-to)1287-1292
Number of pages6
JournalFEBS Letters
Volume585
Issue number9
DOIs
Publication statusPublished - 2011 May 6

Fingerprint

MAP Kinase Kinase Kinase 5
Motor Neurons
Neurons
Stabilization
Proteins
Spinal Muscular Atrophy
SMN Complex Proteins
Small Nuclear Ribonucleoproteins
Ubiquitination
RNA Interference
Phosphotransferases

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Structural Biology

Cite this

Stabilization of the survival motor neuron protein by ASK1. / Kwon, Jeong Eun; Kim, Eun Kyung; Choi, Eui Ju.

In: FEBS Letters, Vol. 585, No. 9, 06.05.2011, p. 1287-1292.

Research output: Contribution to journalArticle

Kwon, Jeong Eun ; Kim, Eun Kyung ; Choi, Eui Ju. / Stabilization of the survival motor neuron protein by ASK1. In: FEBS Letters. 2011 ; Vol. 585, No. 9. pp. 1287-1292.
@article{315151372fa84865bc2aaaa25a79721a,
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}",
year = "2011",
month = "5",
day = "6",
doi = "10.1016/j.febslet.2011.04.011",
language = "English",
volume = "585",
pages = "1287--1292",
journal = "FEBS Letters",
issn = "0014-5793",
publisher = "Elsevier",
number = "9",

}

TY - JOUR

T1 - Stabilization of the survival motor neuron protein by ASK1

AU - Kwon, Jeong Eun

AU - Kim, Eun Kyung

AU - Choi, Eui Ju

PY - 2011/5/6

Y1 - 2011/5/6

N2 - 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).

AB - 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).

KW - Apoptosis signal-regulating kinase 1 (ASK1)

KW - Spinal muscular atrophy (SMA)

KW - Survival motor neuron (SMN)

KW - Ubiquitination

UR - http://www.scopus.com/inward/record.url?scp=79955602279&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955602279&partnerID=8YFLogxK

U2 - 10.1016/j.febslet.2011.04.011

DO - 10.1016/j.febslet.2011.04.011

M3 - Article

VL - 585

SP - 1287

EP - 1292

JO - FEBS Letters

JF - FEBS Letters

SN - 0014-5793

IS - 9

ER -