MYB oncoproteins: emerging players and potential therapeutic targets in human cancer

摘要

The v-myb DNA-binding domain is equivalent to amino acids 72–192 of MYB, except the introduction of four point mutations (I91N, L106H, V117D, and I181V) and the addition of six amino acids in N-terminal region derived from the retroviral Gag polyprotein187. The white dots on AMV v-myb structure indicate point mutations important for the ability of v-myb to transform cells188. MYB co-activators are listed in green and the co-repressors are listed in red. The DNA-binding domain (DBD) is comprised of three repeats (R1, R2, and R3). It is the binding site for a number of proteins including p100, PARP, c-Ski, N-CoR, RAR, Cyp40, C/EMPbeta, SMRT, and mSin3A, as depicted; the central transactivation domain (TAD) is the interaction site for CBP/p300; the negative regulatory domain (NRD) extends from the FAETL motif to the EVES peptide sequence (involved in intramolecular and intermolecular protein–protein interactions) and includes the binding sites for p160/p67, Pin1, and TIF1beta150,189–193. The post-translational modifications include phosphorylation (P), acetylation (AC), and sumoylation (SUMO)194–197.