title: The HTLV-1-encoded protein HBZ directly inhibits the acetyl transferase activity of p300/CBP.
abstract: The homologous cellular coactivators p300 and CBP contain intrinsic lysine acetyl transferase (termed HAT) activity. This activity is responsible for acetylation of several sites on the histones as well as modification of transcription factors. In a previous study, we found that HBZ, encoded by the Human T-cell Leukemia Virus type 1 (HTLV-1), binds to multiple domains of p300/CBP, including the HAT domain. In this study, we found that HBZ inhibits the HAT activity of p300/CBP through the bZIP domain of the viral protein. This effect correlated with a reduction of H3K18 acetylation, a specific target of p300/CBP, in cells expressing HBZ. Interestingly, lower levels of H3K18 acetylation were detected in HTLV-1 infected cells compared to non-infected cells. The inhibitory effect of HBZ was not limited to histones, as HBZ also inhibited acetylation of the NF-κB subunit, p65, and the tumor suppressor, p53. Recent studies reported that mutations in the HAT domain of p300/CBP that cause a defect in acetylation are found in certain types of leukemia. These observations suggest that inhibition of the HAT activity by HBZ is important for the development of adult T-cell leukemia associated with HTLV-1 infection.
authors.affiliation: East Carolina University, Brody School of Medicine, Greenville, NC 27834, USA.
authors.forename: Torsten
authors.initials: T
authors.lastname: Wurm
authors.forename: Diana G
authors.initials: DG
authors.lastname: Wright
authors.forename: Nicholas
authors.initials: N
authors.lastname: Polakowski
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Mesnard
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lemasson
mesh_terms: D000107:Acetylation; D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D003474:Curcumin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D054730:Protein Interaction Domains and Motifs; D012191:Retroviridae Proteins; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology; D014157:Transcription Factors / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D004791:Enzyme Inhibitors; C479751:HBZ protein, human T-cell leukemia virus type I; D006657:Histones; D012191:Retroviridae Proteins; D014157:Transcription Factors; D014764:Viral Proteins; D050880:p300-CBP Transcription Factors; D003474:Curcumin