CREBBP acetylates HINT1 dimer

Histidine Triad Nucleotide-binding protein 1 (HINT1) is a tumor suppressor protein that exerts its function in part by binding to and repressing transcription factors such as MITF and CTNNB1 (beta-catenin) (Razin et al, 1999; Lee et al, 2004; Weiske and Huber, 2005; Genovese et al, 2009). Activity of HINT1 is regulated by post-translational modifications, notably acetylation. CREBBP-dependent acetylation of HINT1 at K21 and K30 disrupts the interaction of HINT1 and MITF, liberating MITF to bind and activate its transcriptional targets (Choudhary et al, 2009; Motzik et al, 2017; Jung et al, 2020; reviewed in Goding and Arnheiter 2019).

组氨酸三联体核苷酸结合蛋白1（HINT1）是一种肿瘤抑制蛋白，其功能部分通过结合并抑制转录因子如MITF和CTNNB1（β-连环蛋白）来实现（Razin等，1999；Lee等，2004；Weiske和Huber，2005；Genovese等，2009）。HINT1的活性受翻译后修饰的调控，尤其是乙酰化修饰。依赖于CREBBP的HINT1在K21和K30位点的乙酰化会破坏HINT1与MITF的相互作用，从而释放MITF以结合并激活其转录靶点（Choudhary等，2009；Motzik等，2017；Jung等，2020；详见Goding和Arnheiter，2019年的综述）。