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J Biol Chem. 2016 Jul 29;291(31):16240-8. doi: 10.1074/jbc.M116.735415. Epub 2016 May 27.

The HIV-1 Tat Protein Is Monomethylated at Lysine 71 by the Lysine Methyltransferase KMT7.

Author information

1
From the Gladstone Institute of Virology and Immunology, San Francisco, California 94158, Departments of Medicine and.
2
From the Gladstone Institute of Virology and Immunology, San Francisco, California 94158.
3
Department of Horticulture, University of Kentucky, Lexington, Kentucky 40508.
4
From the Gladstone Institute of Virology and Immunology, San Francisco, California 94158, Pharmaceutical Frontier Research Laboratory, JT Inc., Yokohama 236-0004, Japan.
5
Pharmaceutical Frontier Research Laboratory, JT Inc., Yokohama 236-0004, Japan.
6
From the Gladstone Institute of Virology and Immunology, San Francisco, California 94158, Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94158.
7
Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109, and.
8
the German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany.
9
From the Gladstone Institute of Virology and Immunology, San Francisco, California 94158, Departments of Medicine and mott@gladstone.ucsf.edu.

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.

KEYWORDS:

human immunodeficiency virus (HIV); post-translational modification (PTM); protein methylation; transcription regulation; viral transcription

PMID:
27235396
PMCID:
PMC4965572
DOI:
10.1074/jbc.M116.735415
[Indexed for MEDLINE]
Free PMC Article

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