Linked Life Data

11959865

Source:http://linkedlifedata.com/resource/pubmed/id/11959865

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
2002-6-24
pubmed:abstractText
Ikaros and Aiolos are Kruppel zinc finger proteins that play key roles in hemo-lymphoid development and homeostasis. We have previously shown that they can repress transcription through the recruitment of histone deacetylases (HDACs). Here, we provide the first functional evidence that these proteins can also repress gene function in a manner that does not require deacetylase activity. This functionality can be attributed in part to Ikaros interactions with the HDAC-independent corepressor, C-terminal binding protein (CtBP). However, mutations that block Ikaros-CtBP interactions do not abolish Ikaros's repression activity, implicating the involvement of additional corepressors. Consistent with this expectation, we show that Ikaros can interact with a CtBP-interacting protein (CtIP), which has also been linked to a deacetylase-independent strategy of repression. Despite being a CtBP interactor, CtIP's association with Ikaros does not require CtBP but instead relies upon its Rb interaction domain. Significantly, Ikaros can interact with Rb, which itself can repress gene function in a deacetylase-independent manner. A mutation in Ikaros that abrogates CtIP interactions significantly reduces repression, and a double mutation that prevents interaction with both CtIP and CtBP even further alleviates repression. Finally, we show that CtIP and CtBP can interact with the general transcription factors, TATA binding protein and transcription factor IIB, which suggests a possible mechanism for their deacetylase-independent mode of repression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Alcohol Oxidoreductases, http://linkedlifedata.com/resource/pubmed/chemical/C-terminal binding protein, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases, http://linkedlifedata.com/resource/pubmed/chemical/Ikaros Transcription Factor, http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins, http://linkedlifedata.com/resource/pubmed/chemical/RBBP8 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, http://linkedlifedata.com/resource/pubmed/chemical/Zfpn1a1 protein, mouse
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
23143-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Ikaros-CtIP interactions do not require C-terminal binding protein and participate in a deacetylase-independent mode of repression.
pubmed:affiliation
Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.