The effects of STAT3 acetylation on the transcriptional activity and tumorigenesis

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that regulate various cellular behaviors, including proliferation, survival, differentiation, metastasis, immune response and metabolism. STAT3 is tightly regulated to maintain a transiently active state in normal cells while persistent STAT3 activation often occurs in cancers. The activated STAT3 undergo several post-translational modifications including phosphorylation, acetylation, methylation, ubiquitination, and SUMOylation, which in turn affect the STAT3 signaling. Due to the important role of STAT3 acetylation in its transcription activity and oncogenesis, targeting STAT3 acetylation may be a potentially therapeutic strategy for human cancers. Although regulation of STAT3 signaling by acetylation has been summarized more than ten years ago, a comprehensive review on STAT3 acetylation and its roles in tumorigenesis as well as its therapeutic implication is missing. In this review, we systematically summarize the recent advances of the role ofSTAT3 acetylation in tumorigenesis. We begin by discussing the process of protein acetylation, then focus on the effect of STAT3 acetylation on the transcriptional activity and its role in carcinogenesis. Lastly, we summarize the recent progress in current development of STAT3 acetylation-related inhibitors. We hope this review will shed light on the critical role of STAT3 acetylation in tumorigenesis, and also provide theoretical basis for future drug design and discovery of STAT3 acetylation-targeting inhibitors.