Gil Jeovanis, Ramírez-Torres Alberto, Encarnación-Guevara Sergio
Programa de Genómica Funcional de Procariontes, Centro de Ciencias Genómicas-UNAM, Av. Universidad s/n, Col. Chamilpa, Cuernavaca, Morelos CP 62210, Mexico.
Programa de Genómica Funcional de Procariontes, Centro de Ciencias Genómicas-UNAM, Av. Universidad s/n, Col. Chamilpa, Cuernavaca, Morelos CP 62210, Mexico.
J Proteomics. 2017 Jan 6;150:297-309. doi: 10.1016/j.jprot.2016.10.003. Epub 2016 Oct 13.
Lysine acetylation is a reversible modification controlled by two groups of enzymes: lysine acetyltransferases (KATs) and lysine deacetylases (KDACs). Acetylated lysine residues are recognized by bromodomains, a family of evolutionarily conserved domains. The use of high-resolution mass spectrometry-based proteomics, in combination with the enrichment of acetylated peptides through immunoprecipitation with anti-acetyl-lysine antibodies, has expanded the number of acetylated proteins from histones and a few nuclear proteins to more than 2000 human proteins. Because acetylation targets almost all cellular processes, this modification has been associated with cancer. Several KATs, KDACs and bromodomain-containing proteins have been linked to cancer development. Many small molecules targeting some of these proteins have been or are being tested as potential cancer therapies. The stoichiometry of lysine acetylation has not been explored in cancer, representing a promising field in which to increase our knowledge of how this modification is affected in cancer. In this review, we will focus on the strategies that can be used to go deeper in the characterization of the protein lysine acetylation emphasizing in cancer research.
赖氨酸乙酰转移酶(KATs)和赖氨酸脱乙酰酶(KDACs)。乙酰化的赖氨酸残基由溴结构域识别,溴结构域是一类进化上保守的结构域家族。基于高分辨率质谱的蛋白质组学技术,结合使用抗乙酰赖氨酸抗体通过免疫沉淀富集乙酰化肽段,已将乙酰化蛋白质的数量从组蛋白和少数核蛋白扩展到2000多种人类蛋白质。由于乙酰化几乎靶向所有细胞过程,这种修饰已与癌症相关联。几种KATs、KDACs和含溴结构域的蛋白质已与癌症发展相关。许多靶向其中一些蛋白质的小分子已作为潜在的癌症治疗方法进行了测试或正在测试中。赖氨酸乙酰化的化学计量在癌症中尚未得到探索,这是一个有前景的领域,有助于增加我们对这种修饰在癌症中如何受到影响的认识。在本综述中,我们将重点关注可用于更深入表征蛋白质赖氨酸乙酰化的策略,重点是癌症研究。