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 cycle and development. It functions through a direct interaction with protein factors involved in cell cycle progression and differentiation. In the present study we characterized a novel Rb-associated protein, Cream1, which bound to Rb specifically through a C-terminal region. Cream1 contained 959 amino 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 signal resembling that of the large T antigen of simian virus 40. Its primary sequence 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. Cream1 exhibited an activation activity that was attributed to its N-terminal portion when assayed in yeast. Its relationship with the muscle-enhancer-binding protein MusTRD1 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 Williams' syndrome, a neurodevelopmental disease with multisystem abnormalities, implying its involvement in certain disorders. Taken together, our results suggest that Cream1 might serve as a positive transcription regulator under the control of Rb.
Yan
X
X
Shanghai Research Center of Life Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
Zhao
X
X
Qian
M
M
Guo
N
N
Gong
X
X
Zhu
X
X
D000595:Amino Acid Sequence; D000818:Animals; D002897:Chromosomes, Human, Pair 7; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009124:Muscle Proteins; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D018980:Williams Syndrome / Q000235:genetics*
D004268:DNA-Binding Proteins; C405493:GTF2IRD1 protein, human; D009124:Muscle Proteins; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein; D015534:Trans-Activators; D014157:Transcription Factors