Linked Life Data

21336309

Source:http://linkedlifedata.com/resource/pubmed/id/21336309

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-3-2
pubmed:abstractText
The ERK (extracellular signal-regulated kinase) MAPK (mitogen-activated protein kinase) cascade (Raf-MEK-ERK) mediates mitogenic signalling, and is frequently hyperactivated by Ras oncogenes in human cancer. The entire range of activities of multifunctional Ras in carcinogenesis remains elusive. Here we report that the ERK pathway is downregulated by MEK (MAPK-ERK kinase) SUMOylation, which is inhibited by oncogenic Ras. MEK SUMOylation blocked ERK activation by disrupting the specific docking interaction between MEK and ERK. Expression of un-SUMOylatable MEK enhanced ERK activation, cell differentiation, proliferation and malignant transformation by oncogenic ErbB2 or Raf, but not by active Ras. Interestingly, MEK SUMOylation was abrogated in cancer cells harbouring Ras mutations. Oncogenic Ras inhibits MEK SUMOylation by impairing the function of the MEKK1 MAPKKK as a SUMO-E3 ligase specific for MEK. Furthermore, forced enhancement of MEK SUMOylation suppressed Ras-induced cell transformation. Thus, oncogenic Ras efficiently activates the ERK pathway both by activating Raf and by inhibiting MEK SUMOylation, thereby inducing carcinogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1476-4679
pubmed:author
pubmed:copyrightInfo
© 2011 Macmillan Publishers Limited. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
282-91
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Oncogenic Ras abrogates MEK SUMOylation that suppresses the ERK pathway and cell transformation.
pubmed:affiliation
Department of Molecular Cell Signaling, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Tokyo 108-8639, Japan..
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't