GCN5, conserved from yeast to humans, and the vertebrate specific PCAF, are lysine acetyltransferase enzymes found in large protein complexes. Both enzymes have well documented roles in the histone acetylation and the concomitant regulation of transcription. However, these enzymes also acetylate non-histone substrates to impact diverse aspects of cell physiology. Here, I review our current understanding of non-histone acetylation by GCN5 and PCAF across eukaryotes, from target identification to molecular mechanism and regulation. I focus mainly on budding yeast, where Gcn5 was first discovered, and mammalian systems, where the bulk of non-histone substrates have been characterized. I end the review by defining critical caveats and open questions that apply to all models.

从酵母到人类保守的GCN5，以及脊椎动物特有的PCAF，是在大型蛋白质复合物中发现的赖氨酸乙酰基转移酶。两种酶在组蛋白乙酰化和转录的伴随调节中均具有充分文献记载的作用。但是，这些酶也会乙酰化非组蛋白底物，从而影响细胞生理的各个方面。在这里，我回顾了我们目前对跨真核生物通过GCN5和PCAF进行的非组蛋白乙酰化的了解，从靶标识别到分子机制和调控。我主要关注最初发现Gcn5的发芽酵母和已鉴定出大量非组蛋白底物特征的哺乳动物系统。我通过定义关键的警告和适用于所有模型的开放性问题来结束本评论。