Distinct localizations and repression activities of MM-1 isoforms toward c-Myc.

MM-1 was identified as a c-Myc-binding protein and has been reported to repress the E-box-dependent transcription activity of c-Myc by recruiting HDAC1 complex via TIF1 beta/KAP1. In this study, originally isolated MM-1 was found to be a fusion protein comprised of the N-terminal 13 amino acids from the sequence of chromosome 14 and of the rest of the amino acids from that of chromosome 12 and was found to be expressed ubiquitously in all human tissues. Four splicing isoforms of MM-1, MM-1alpha, MM-1beta, MM-1gamma, and MM-1delta, which are derived from the sequence of chromosome 12, were then identified. Of these isoforms, MM-1alpha, MM-1gamma, and MM-1delta were found to be expressed in tissue-specific manners and MM-1beta was found to be expressed ubiquitously. Although all of the isoforms potentially possessed c-Myc- and TIF1beta-binding activities, MM-1beta and MM-1delta were found to be mainly localized in the cytoplasm and MM-1alpha and MM-1gamma were found to be localized in the nucleus together with both c-Myc and TIF1beta. Furthermore, when repression activities of MM-1 isoforms toward c-Myc transcription activity were examined by reporter gene assays in HeLa cells, MM-1alpha, MM-1gamma, and MM-1gamma, but not MM-1beta, were found to repress transcription activity of c-Myc, and the degrees of repression by MM-1gamma and MM-1delta were smaller than those by MM-1 and MM-1alpha. These results suggest that each MM-1 isoform distinctly regulates c-Myc transcription activity in respective tissues.