Cyclin A and the retinoblastoma gene product complex with a common transcription factor.
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.
Bandara
L R
LR
Laboratory of Eukaryotic Molecular Genetics, MRC National Institute for Medical Research, Mill Hill, London, UK.
Adamczewski
J P
JP
Hunt
T
T
La Thangue
N B
NB
D000818:Animals; D002352:Carrier Proteins; D002417:Cattle; D018797:Cell Cycle Proteins; D002460:Cell Line; D016213:Cyclins / Q000302:isolation & purification / Q000378:metabolism*; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D016161:Genes, Retinoblastoma; D007118:Immunoassay; D046911:Macromolecular Substances; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000302:isolation & purification / Q000378:metabolism*; D056465:Retinoblastoma-Binding Protein 1; D014157:Transcription Factors / Q000302:isolation & purification / Q000378:metabolism*
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D046911:Macromolecular Substances; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D014157:Transcription Factors