BAF53 forms distinct nuclear complexes and functions as a critical c-Myc-interacting nuclear cofactor for oncogenic transformation.
The c-Myc oncoprotein functions as a transcription factor that can transform normal cells into tumor cells, as well as playing a direct role in normal cell proliferation. The c-Myc protein transactivates cellular promoters by recruiting nuclear cofactors to chromosomal sites through an N-terminal transactivation domain. We have previously reported the identification and functional characterization of four different c-Myc cofactors: TRRAP, hGCN5, TIP49, and TIP48. Here we present the identification and characterization of the actin-related protein BAF53 as a c-Myc-interacting nuclear cofactor that forms distinct nuclear complexes. In addition to the human SWI/SNF-related BAF complex, BAF53 forms a complex with TIP49 and TIP48 and a separate biochemically distinct complex containing TRRAP and a histone acetyltransferase which does not contain TIP60. Using deletion mutants of BAF53, we show that BAF53 is critical for c-Myc oncogenic activity. Our results indicate that BAF53 plays a functional role in c-Myc-interacting nuclear complexes.
Park
Jeonghyeon
J
Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544-1014, USA.
Wood
Marcelo A
MA
Cole
Michael D
MD
D000074183:ATPases Associated with Diverse Cellular Activities; D000123:Acetyltransferases / Q000378:metabolism; D000199:Actins / Q000235:genetics / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone; D004265:DNA Helicases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006657:Histones / Q000032:analysis; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D009707:Nucleosomes / Q000737:chemistry; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000378:metabolism*
C116160:ACTL6A protein, human; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006657:Histones; D009687:Nuclear Proteins; D009707:Nucleosomes; D016271:Proto-Oncogene Proteins c-myc; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C113829:transformation-transcription domain-associated protein; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C486549:RUVBL1 protein, human; C122079:RUVBL2 protein, human