Transcriptional inhibition by the retinoblastoma protein

1993 ◽  
Vol 340 (1293) ◽  
pp. 333-336 ◽  
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Retinoblastoma Protein ◽  
Specific Cell ◽  
Retinoblastoma Gene ◽  
Transcriptional Inhibition ◽  
Human Tumours ◽  
E2f Transcription Factor ◽  
Cycle Dependent ◽  
Regulation Of Cell Cycle

The retinoblastoma protein, pRB, appears to play a key role in coordinating the regulation of cell cycle position and transcriptional events. pRB undergoes specific cell-cycle-dependent phosphorylation, being underphosphorylated in G1 and heavily phosphorylated in S, G2, and M. The underphosphorylated form is able to interact with the E2F transcription factor. Recently, we have cloned a cDNA for E2F-1. By using this clone and a series of non-pRB binding mutants, we have been able to show that the binding of pRB to E2F-1 causes inhibition of E2F-mediated transactivation. pRB ’s inhibition of E2F-mediated transcription would be lost by mutation in the retinoblastoma gene in human tumours, by pRB s interaction with DNA tumour virus oncoproteins, or by phosphorylation during the cell cycle.

scholarly journals Regulation of Cell Cycle-Specific Gene Expression through Cyclin-Dependent Kinase-Mediated Phosphorylation of the Forkhead Transcription Factor Fkh2p

2004 ◽  
Vol 24 (22) ◽  
pp. 10036-10046 ◽  
Author(s):  
Aline Pic-Taylor ◽  
Zoulfia Darieva ◽  
Brian A. Morgan ◽  
Andrew D. Sharrocks
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Specific Gene ◽  
Cyclin Dependent Kinase ◽  
Forkhead Transcription Factor ◽  
Cyclin Dependent Kinases ◽  
Regulated Expression ◽  
Dependent Protein ◽  
Cycle Dependent ◽  
Regulation Of Cell Cycle

ABSTRACT The forkhead transcription factor Fkh2p acts in a DNA-bound complex with Mcm1p and the coactivator Ndd1p to regulate cell cycle-dependent expression of the CLB2 gene cluster in Saccharomyces cerevisiae. Here, we demonstrate that Fkh2p is a target of cyclin-dependent protein kinases and that phosphorylation of Fkh2p promotes interactions between Fkh2p and the coactivator Ndd1p. These phosphorylation-dependent changes in the Fkh2p-Ndd1p complex play an important role in the cell cycle-regulated expression of the CLB2 cluster. Our data therefore identify an important regulatory target for cyclin-dependent kinases in the cell cycle and further our molecular understanding of the key cell cycle regulatory transcription factor Fkh2p.

Identification of distinct roles for separate E1A domains in disruption of E2F complexes

1993 ◽  
Vol 13 (11) ◽  
pp. 7029-7035
Author(s):  
M A Ikeda ◽  
J R Nevins
Keyword(s):  
Transcription Factor ◽  
Gene Product ◽  
Protein Complexes ◽  
Cyclin A ◽  
Regulatory Proteins ◽  
Retinoblastoma Gene ◽  
Adenovirus E1a ◽  
E2f Transcription Factor ◽  
Cdk2 Complex ◽  
Equilibrium Dissociation

The adenovirus E1A protein can disrupt protein complexes containing the E2F transcription factor in association with cellular regulatory proteins such as the retinoblastoma gene product (Rb) and the Rb-related p107 protein. Previous experiments have shown that the CR1 and CR2 domains of E1A are required for this activity. We now demonstrate that the CR2 domain is essential for allowing E1A to interact with the E2F-Rb or the E2F-p107-cyclin A-cdk2 complex. Multimeric complexes containing E1A can be detected when the CR1 domain has been rendered inactive by mutation. In addition, the E1A CR1 domain, but not the CR2 domain, is sufficient to prevent the interaction of E2F with Rb or p107. On the basis of these results, we suggest a model whereby the CR2 domain brings E1A to the E2F complexes and then, upon a normal equilibrium dissociation of Rb or p107 from E2F, the E1A CR1 domain is able to block the site of interaction on Rb or p107, thereby preventing the re-formation of the complexes.

scholarly journals The retinoblastoma gene product is a cell cycle-dependent, nuclear matrix-associated protein.

1994 ◽  
Vol 91 (1) ◽  
pp. 418-422 ◽  
Author(s):  
M. A. Mancini ◽  
B. Shan ◽  
J. A. Nickerson ◽  
S. Penman ◽  
W. H. Lee
Keyword(s):  
Cell Cycle ◽  
Gene Product ◽  
Nuclear Matrix ◽  
Retinoblastoma Gene ◽  
A Cell ◽  
Retinoblastoma Gene Product ◽  
Cycle Dependent

scholarly journals Ste12 and Mcm1 regulate cell cycle-dependent transcription of FAR1.

1996 ◽  
Vol 16 (6) ◽  
pp. 2830-2837 ◽  
Author(s):  
L J Oehlen ◽  
J D McKinney ◽  
F R Cross
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Transcriptional Activation ◽  
G1 Phase ◽  
Protein Accumulation ◽  
Transcriptional Activation Domain ◽  
Cycle Arrest ◽  
Gal1 Promoter ◽  
Combinatorial Control ◽  
Cycle Dependent

The transcripts of many genes involved in Saccharomyces cerevisiae mating were found to fluctuate during the cell cycle. In the absence of a functional Ste12 transcription factor, both the levels and the cell cycle pattern of expression of these genes were affected. FUS1 and AGA1 levels, which are maximally expressed only in G1-phase cells, were strongly reduced in ste12- cells. The cell cycle transcription pattern for FAR1 was changed in ste12- cells: the gene was still significantly expressed in G2/M, but transcript levels were strongly reduced in G1 phase, resulting in a lack of Far1 protein accumulation. G2/M transcription of FAR1 was dependent on the transcription factor Mcm1, and expression of a gene with Mcm1 fused to a strong transcriptional activation domain resulted in increased levels of FAR1 transcription. The pattern of cell cycle-regulated transcription of FAR1 could involve combinatorial control of Ste12 and Mcm1. Forced G1 expression of FAR1 from the GAL1 promoter resorted the ability to arrest in response to pheromone in ste12-cells. This indicates that transcription of FAR1 in the G1 phase is essential for accumulation of the protein and for pheromone-induced cell cycle arrest.

The Retinoblastoma Protein Region Required for Interaction with the E2F Transcription Factor Includes the T/E1A Binding and Carboxy-Terminal Sequences

1992 ◽  
Vol 11 (7) ◽  
pp. 539-548 ◽  
Author(s):  
SHI HUANG ◽  
ELINOR SHIN ◽  
KELLY-ANN SHEPPARD ◽  
LINDA CHOKROVERTY ◽  
BEI SHAN ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Retinoblastoma Protein ◽  
E2f Transcription Factor ◽  
Carboxy Terminal
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