The HIV-1 Tat Protein Is Monomethylated at Lysine 71 by the Lysine Methyltransferase KMT7
The HIV-1 Tat Protein Is Monomethylated at Lysine 71 by the Lysine Methyltransferase KMT7
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DOI：
10.1074/jbc.m116.735415
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发表时间：
2016-07-29
影响因子：
4.8
通讯作者：
Ott, Melanie
中科院分区：
文献类型：
--
作者：
Ali, Ibraheem;Ramage, Holly;Ott, Melanie
HIV-1反式激活蛋白Tat是HIV转录的关键调节因子，主要是使病毒转录本有效延长。它与RNA和各种宿主因子的相互作用受到有序的、瞬时的翻译后修饰的调节。在这里，我们报道了一种新的TAT修饰，单甲基化赖氨酸-71(K71)。我们发现，Lys-71单甲基化(K71me)是由KMT7催化的，KMT7是一种甲基转移酶，也针对TAT中的赖氨酸51(K51)。利用质谱学、体外酶学和修饰特异性抗体，我们发现KMT7单甲基化TAT中的Lys-71和Lys-51。K71me对于完整的TAT反式激活是重要的，因为KMT7基因敲除会削弱野生型(WT)TAT的转录活性，但不会损害TAT K71R突变体的转录活性。这些发现强调了KMT7作为一种重要的单甲基转移酶通过TAT调节HIV转录的作用。
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, monomethylationatlysine-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.