Characterization and gene structure of a novel retinoblastoma-protein-associated protein similar to the transcription regulator TFII-I

Retinoblastoma protein (Rb) is an important regulator of vertebrate cell cy cle and development. It functions through a direct interaction with protein factors involved in cell cycle progression and differentiation. In the pre sent study we characterized a novel Rb-associated protein, Cream1, which bo und to Rb specifically through a C-terminal region. Cream1 contained 959 am ino acid residues and migrated as a protein of approx. 120 kDa on SDS/PAGE, It was a widely expressed nuclear protein with a nuclear localization sign al resembling that of the large T antigen of simian virus 40, Its primary s equence was characteristic of five direct repeats that were similar to, but distinct from, those of TFII-I, a multifunctional transcription regulator. Three additional regions were also highly conserved in both proteins. Crea m1 exhibited an activation activity that was attributed to its N-terminal p ortion when assayed in yeast. Its relationship with the muscle-enhancer-bin ding protein Mus-TRD1 further suggests a role in regulating gene expression . The structural gene, CREAM1, contained 27 exons and spanned more than 150 kb. It was located at human chromosome 7q11.23 in a region deleted for Wil liams' syndrome, a neurodevelopmental disease with multisystem abnormalitie s, implying its involvement in certain disorders. Taken together, our resul ts suggest that Cream1 might serve as a positive transcription regulator un der the control of Rb.