Article: Identification and characterization of EBP, a novel EEN binding protein that inhibits Ras signaling and is recruited into the nucleus by the MLL-EEN fusion protein

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TitleIdentification and characterization of EBP, a novel EEN binding protein that inhibits Ras signaling and is recruited into the nucleus by the MLL-EEN fusion protein
AuthorsYam, JWP
Jin, DY
So, CW
Chan, LC1
KeywordsCarrier Proteins - chemistry - genetics - metabolism
DNA-Binding Proteins - genetics - metabolism
Nucleocytoplasmic Transport Proteins
Proto-Oncogenes
Steroid Isomerases
Issue Date2004
PublisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
CitationBlood, 2004, v. 103 n. 4, p. 1445-1453 [How to Cite?]
DOI: http://dx.doi.org/10.1182/blood-2003-07-2452
AbstractThe chimeric MLL-EEN fusion protein is created as a result of chromosomal translocation t(11;19)(q23;p13). EEN, an Src homology 3 (SH3) domain-containing protein in the endophilin family, has been implicated in endocytosis, although little is known about its role in leukemogenesis mediated by the MLL-EEN fusion protein. In this study, we have identified and characterized EBP, a novel EEN binding protein that interacts with the SH3 domain of EEN through a proline-rich motif PPERP. EBP is a ubiquitous protein that is normally expressed in the cytoplasm but is recruited to the nucleus by MLL-EEN with a punctate localization pattern characteristic of the MLL chimeric proteins. EBP interacts simultaneously with EEN and Sos, a guanine-nucleotide exchange factor for Ras. Coexpressoin of EBP with EEN leads to suppression of Ras-induced cellular transformation and Ras-mediated activation of Elk-1. Taken together, our findings suggest a new mechanism for MLL-EEN-mediated leukemogenesis in which MLL-EEN interferes with the Ras-suppressing activities of EBP through direct interaction. © 2004 by The American Society of Hematology.
ISSN0006-4971
2011 Impact Factor: 9.898
2011 SCImago Journal Rankings: 1.698
DOIhttp://dx.doi.org/10.1182/blood-2003-07-2452
ISI Accession Number IDWOS:000188828200046
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorYam, JWP
dc.contributor.authorJin, DY
dc.contributor.authorSo, CW
dc.contributor.authorChan, LC
dc.date.accessioned2008-05-22T04:15:24Z
dc.date.available2008-05-22T04:15:24Z
dc.date.issued2004
dc.description.abstractThe chimeric MLL-EEN fusion protein is created as a result of chromosomal translocation t(11;19)(q23;p13). EEN, an Src homology 3 (SH3) domain-containing protein in the endophilin family, has been implicated in endocytosis, although little is known about its role in leukemogenesis mediated by the MLL-EEN fusion protein. In this study, we have identified and characterized EBP, a novel EEN binding protein that interacts with the SH3 domain of EEN through a proline-rich motif PPERP. EBP is a ubiquitous protein that is normally expressed in the cytoplasm but is recruited to the nucleus by MLL-EEN with a punctate localization pattern characteristic of the MLL chimeric proteins. EBP interacts simultaneously with EEN and Sos, a guanine-nucleotide exchange factor for Ras. Coexpressoin of EBP with EEN leads to suppression of Ras-induced cellular transformation and Ras-mediated activation of Elk-1. Taken together, our findings suggest a new mechanism for MLL-EEN-mediated leukemogenesis in which MLL-EEN interferes with the Ras-suppressing activities of EBP through direct interaction. © 2004 by The American Society of Hematology.
dc.description.naturepostprint
dc.format.extent146861 bytes
dc.format.extent3021 bytes
dc.format.mimetypeapplication/pdf
dc.format.mimetypetext/plain
dc.identifier.citationBlood, 2004, v. 103 n. 4, p. 1445-1453 [How to Cite?]
DOI: http://dx.doi.org/10.1182/blood-2003-07-2452
dc.identifier.doihttp://dx.doi.org/10.1182/blood-2003-07-2452
dc.identifier.epage1453
dc.identifier.hkuros86076
dc.identifier.isiWOS:000188828200046
dc.identifier.issn0006-4971
2011 Impact Factor: 9.898
2011 SCImago Journal Rankings: 1.698
dc.identifier.issue4
dc.identifier.openurl
dc.identifier.pmid14551139
dc.identifier.scopuseid_2-s2.0-0842307321
dc.identifier.spage1445
dc.identifier.urihttp://hdl.handle.net/10722/48499
dc.identifier.volume103
dc.languageeng
dc.publisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
dc.publisher.placeUnited States
dc.relation.ispartofBlood
dc.relation.referencesReferences in Scopus
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
dc.subjectCarrier Proteins - chemistry - genetics - metabolism
dc.subjectDNA-Binding Proteins - genetics - metabolism
dc.subjectNucleocytoplasmic Transport Proteins
dc.subjectProto-Oncogenes
dc.subjectSteroid Isomerases
dc.titleIdentification and characterization of EBP, a novel EEN binding protein that inhibits Ras signaling and is recruited into the nucleus by the MLL-EEN fusion protein
dc.typeArticle
Author Affiliations
  1. Queen Mary Hospital Hong Kong