title: And-1 is required for the stability of histone acetyltransferase Gcn5.
abstract: Histone acetyltransferases (HATs) have a central role in the modification of chromatin as well as in the pathogenesis of a broad set of diseases including cancers. Gcn5 is the first identified transcription-related HAT that has been implicated in the regulation of diverse cellular functions. However, how Gcn5 proteins are regulated remains largely unknown. Here we show that acidic nucleoplasmic DNA-binding protein (And-1, a high mobility group domain-containing protein) has remarkable capability to regulate the stability of Gcn5 proteins and thereby histone H3 acetylation. We find that And-1 forms a complex with both histone H3 and Gcn5. Downregulation of And-1 results in Gcn5 degradation, leading to the reduction of H3K9 and H3K56 acetylation. And-1 overexpression stabilizes Gcn5 through protein-protein interactions in vivo. Furthermore, And-1 expression is increased in cancer cells in a manner correlating with increased Gcn5 and H3K9Ac and H3K56Ac. Thus, our data reveal not only a functional link between Gcn5 and And-1 that is essential for Gcn5 protein stability and histone H3 acetylation, but also a potential role of And-1 in cancer.
authors: Department of Biochemistry and Molecular Biology, The George Washington University Medical School, Washington, DC 20037, USA.
authors: Y
authors: Y
authors: Li
authors: A N
authors: AN
authors: Jaramillo-Lambert
authors: Y
authors: Y
authors: Yang
authors: R
authors: R
authors: Williams
authors: N H
authors: NH
authors: Lee
authors: W
authors: W
authors: Zhu
mesh_terms: D000107:Acetylation; D002453:Cell Cycle; D002460:Cell Line; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D045325:HCT116 Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008239:Lysine / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D055550:Protein Stability; D034622:RNA Interference; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; D008239:Lysine; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C544202:WDHD1 protein, human