Linked Life Data

19576169

Source:http://linkedlifedata.com/resource/pubmed/id/19576169

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-7-31
pubmed:abstractText
Mutations in the Cu,Zn-superoxide dismutase (SOD1) gene cause 20-25% of familial amyotrophic lateral sclerosis (ALS). Mutant SOD1 causes motor neuron degeneration through toxic gain-of-function(s). However, the direct molecular targets of mutant SOD1, underlying its toxicity, are not fully understood. In this study, we found that alpha/beta-tubulin is one of the major mutant SOD1-interacting proteins, but that wild-type SOD1 does not interact with it. The interaction between tubulin and mutant SOD1 was detected in the spinal cords of mutant G93A SOD1 transgenic mice before the onset of symptoms. Tubulin interacted with amino acid residues 1-23 and 116-153 of SOD1. Overexpression of mutant SOD1 resulted in the accumulation of tubulin in detergent-insoluble fractions. In a cell-free system, mutant SOD1 modulated tubulin polymerization, while wild-type SOD1 did not. Since tightly regulated microtubule dynamics is essential for neurons to remain viable, alpha/beta-tubulin could be an important direct target of mutant SOD1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1090-2104
pubmed:author
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
387
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
121-6
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Familial amyotrophic lateral sclerosis-linked mutant SOD1 aberrantly interacts with tubulin.
pubmed:affiliation
Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan. kabuta@ncnp.go.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't