Post-translational modification of retinoic acid receptor alpha and its roles in tumor cell differentiation

Retinoic acid (RA) is a well-known differentiation inducer that exerts its effects by binding to nuclear RA receptors. Retinoic acid receptor alpha (RAR alpha), as an important nuclear RA receptor, is activated upon RA binding and facilitates the transcription of target genes related to differentiation, which ultimately initiates cell differentiation. Previous studies have found that the transcriptional activity of RAR alpha is regulated by various post-translational modifications, which influence its DNA binding efficiency, transactivation ability and even lead to degradation. Post-translational modifications of RAR alpha, as a consequence, play an important role in the RA-induced differentiation process. Therefore, in this review, we focus on recent advances in the understanding of how these modifications affect the activity of RAR alpha as well as strategies to increase the differentiation effect of RA treatment in cancer cells based on RAR alpha modifications, which may promote the development of novel effective differentiation therapies for cancer treatment.