Identification of PP2A as a novel interactor and regulator of TRIP-Br1
Data(s) |
01/01/2009
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Resumo |
TRIP-Br proteins area novel family of transcriptional coregulators involved in E2F-mediated cell cycle progression. Three of the four mammalian members of TRIP-Br family, including TRIP-Br1, are known oncogenes. We now report the identification of the Bot regulatory subunit of serine/threonine protein phosphatase 2A (MA) as a novel TRIP-Br1 interactor, based on an affinity binding assay coupled with mass spectrometry. A GST-TRIP-Br1 fusion protein associates with catalytically active PP2A-AB alpha C holoenzyme in vitro. Coimmunoprecipitation confirms this association in vivo. Immunofluorescence staining with a monoclonal antibody against TRIP-Br1 reveals that endogenous TRIP-Br1 and PP2A-B alpha colocalize mainly in the cytoplasm. Consistently, immunoprecipitation followed by immunodetection with anti-phosphoserine antibody suggest that TRIP-Br1 exists in a serine-phosphorylated form. Inhibition of PP2A activity by okadaic acid or transcriptional silencing of the PP2A catalytic subunit by small interfering RNA results in downregulation of total TRIP-Br1 protein levels but upregulation of serine-phosphorylated TRIP-Br1. Overexpression of PP2A catalytic subunit increases TRIP-Br1 protein levels and TRIP-Br1 co-activated E2F1/DP1 transcription. Our data support a model in which association between PP2A-AB alpha C holoenzyme and TRIP-Br1 in vivo in mammalian cells represents a novel mechanism for regulating the level of TRIP-Br1 protooncoprotein. (C) 2008 Elsevier Inc. All rights reserved. |
Identificador | |
Idioma(s) |
eng |
Direitos |
info:eu-repo/semantics/restrictedAccess |
Fonte |
Zang , Z J , Gunaratnam , L , Cheong , J K , Lai , L Y , Hsiao , L L , O'Leary , E , Sun , X M , Salto-Tellez , M , Bonventre , J V & Hsu , S I H 2009 , ' Identification of PP2A as a novel interactor and regulator of TRIP-Br1 ' Cellular Signalling , vol 21 , no. 1 , pp. 34-42 . DOI: 10.1016/j.cellsig.2008.09.018 |
Palavras-Chave | #/dk/atira/pure/subjectarea/asjc/1300/1307 #Cell Biology |
Tipo |
article |