title: The HIV-1 Tat Protein Is Monomethylated at Lysine 71 by the Lysine Methyltransferase KMT7.
abstract: The HIV-1 transactivator protein Tat is a critical regulator of HIV transcription primarily enabling efficient elongation of viral transcripts. Its interactions with RNA and various host factors are regulated by ordered, transient post-translational modifications. Here, we report a novel Tat modification, monomethylation at lysine 71 (K71). We found that Lys-71 monomethylation (K71me) is catalyzed by KMT7, a methyltransferase that also targets lysine 51 (K51) in Tat. Using mass spectrometry, in vitro enzymology, and modification-specific antibodies, we found that KMT7 monomethylates both Lys-71 and Lys-51 in Tat. K71me is important for full Tat transactivation, as KMT7 knockdown impaired the transcriptional activity of wild type (WT) Tat but not a Tat K71R mutant. These findings underscore the role of KMT7 as an important monomethyltransferase regulating HIV transcription through Tat.
authors.affiliation: From the Gladstone Institute of Virology and Immunology, San Francisco, California 94158, Departments of Medicine and.
authors.forename: Ibraheem
authors.initials: I
authors.lastname: Ali
authors.affiliation: From the Gladstone Institute of Virology and Immunology, San Francisco, California 94158.
authors.forename: Holly
authors.initials: H
authors.lastname: Ramage
authors.affiliation: From the Gladstone Institute of Virology and Immunology, San Francisco, California 94158.
authors.forename: Daniela
authors.initials: D
authors.lastname: Boehm
authors.affiliation: Department of Horticulture, University of Kentucky, Lexington, Kentucky 40508.
authors.forename: Lynnette M A
authors.initials: LM
authors.lastname: Dirk
authors.affiliation: From the Gladstone Institute of Virology and Immunology, San Francisco, California 94158, Pharmaceutical Frontier Research Laboratory, JT Inc., Yokohama 236-0004, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sakane
authors.affiliation: Pharmaceutical Frontier Research Laboratory, JT Inc., Yokohama 236-0004, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Hanada
authors.affiliation: From the Gladstone Institute of Virology and Immunology, San Francisco, California 94158.
authors.forename: Sara
authors.initials: S
authors.lastname: Pagans
authors.affiliation: From the Gladstone Institute of Virology and Immunology, San Francisco, California 94158.
authors.forename: Katrin
authors.initials: K
authors.lastname: Kaehlcke
authors.affiliation: From the Gladstone Institute of Virology and Immunology, San Francisco, California 94158, Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158.
authors.forename: Katherine
authors.initials: K
authors.lastname: Aull
authors.affiliation: From the Gladstone Institute of Virology and Immunology, San Francisco, California 94158, Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158.
authors.forename: Leor
authors.initials: L
authors.lastname: Weinberger
authors.affiliation: Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, and.
authors.forename: Raymond
authors.initials: R
authors.lastname: Trievel
authors.affiliation: the German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Schnoelzer
authors.affiliation: Pharmaceutical Frontier Research Laboratory, JT Inc., Yokohama 236-0004, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kamada
authors.affiliation: Department of Horticulture, University of Kentucky, Lexington, Kentucky 40508.
authors.forename: Robert
authors.initials: R
authors.lastname: Houtz
authors.affiliation: From the Gladstone Institute of Virology and Immunology, San Francisco, California 94158, Departments of Medicine and mott@gladstone.ucsf.edu.
authors.forename: Melanie
authors.initials: M
authors.lastname: Ott
mesh_terms: D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D008745:Methylation; D015533:Transcriptional Activation; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D054322:tat Gene Products, Human Immunodeficiency Virus; D011495:Histone-Lysine N-Methyltransferase; C540312:SETD7 protein, human; D008239:Lysine
keywords: human immunodeficiency virus (HIV); post-translational modification (PTM); protein methylation; transcription regulation; viral transcription