Cyclin A and the retinoblastoma gene product complex with a common transcription factor

• Published in: Nature (London) 1991-07, Vol.352 (6332), p.249-251
• Main Authors: Bandara, Lasantha R, Adamczewski, Jörg P, Hunt, Tim, La Thangue, Nicholas B
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Carrier Proteins; Cattle; Cell Cycle Proteins; Cell Line; Cellular biology; Cyclins - isolation & purification; Cyclins - metabolism; DNA-Binding Proteins; DRTF1 protein; E2F Transcription Factors; Fundamental and applied biological sciences. Psychology; Genes, Retinoblastoma; Genetics; Immunoassay; Macromolecular Substances; Medical research; Molecular and cellular biology; Molecular genetics; Proteins; Recombinant Proteins - isolation & purification; Recombinant Proteins - metabolism; retinoblastoma; Retinoblastoma Protein - isolation & purification; Retinoblastoma Protein - metabolism; Retinoblastoma-Binding Protein 1; Transcription Factors - isolation & purification; Transcription Factors - metabolism; Transcription. Transcription factor. Splicing. Rna processing
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/352249a0

The retinoblastoma gene (Rb) product is a negative regulator of cellular proliferation, an effect that could be mediated in part at the transcriptional level through its ability to complex with the sequence-specific transcription factor DRTF1. This interaction is modulated by adenovirus E1a, which sequesters the Rb protein and several other cellular proteins, including cyclin A, a molecule that undergoes cyclical accumulation and destruction during each cell cycle and which is required for cell cycle progression. Cyclin A, which also complexes with DRTF1, facilitates the efficient assembly of the Rb protein into the complex. This suggests a role for cyclin A in regulating transcription and defines a transcription factor through which molecules that regulate the cell cycle in a negative fashion, such as Rb, and in a positive fashion, such as cyclin A, interact. Mutant loss-of-function Rb alleles, which occur in a variety of tumour cells, also fail to complex with E1a and large T antigen. Here we report on a naturally occurring loss-of-function Rb allele encoding a protein that fails to complex with DRTF1. This might explain how mutation in the Rb gene prevents negative growth control.