ATM is involved in cell-cycle control through the regulation of retinoblastoma protein phosphorylation

2010 ◽  
pp. n/a-n/a ◽  
Author(s):  
Javier G. Pizarro ◽  
Jaume Folch ◽  
Aurelio Vazquez de la Torre ◽  
Felix Junyent ◽  
Ester Verdaguer ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Phosphorylation ◽  
Cell Cycle Control ◽  
Retinoblastoma Protein

Cell Cycle Control by Ataxia Telangiectasia Mutated Protein Through Regulating Retinoblastoma Protein Phosphorylation

2012 ◽  
pp. 103-115
Author(s):  
Javier G. Pizarro ◽  
Antoni Camins ◽  
Felix Junyent ◽  
Ester Verdaguer ◽  
Carme Auladell ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Phosphorylation ◽  
Ataxia Telangiectasia ◽  
Cell Cycle Control ◽  
Retinoblastoma Protein ◽  
Ataxia Telangiectasia Mutated ◽  
Ataxia Telangiectasia Mutated Protein

Retinoblastoma Protein, Gene Expression, and Cell Cycle Control

Cancer Genes ◽  
1996 ◽  
pp. 177-191
Author(s):  
Jane Clifford Azizkhan ◽  
Shiaw Yih Lin ◽  
David Jensen ◽  
Dusan Kostic ◽  
Adrian R. Black
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Protein Gene ◽  
Cell Cycle Control ◽  
Retinoblastoma Protein

Integration of cell cycle control with transcriptional regulation by the retinoblastoma protein

1993 ◽  
Vol 5 (2) ◽  
pp. 194-200 ◽  
Author(s):  
Robert E. Hollingsworth ◽  
Phang-Lang Chen ◽  
Wen-Hwa Lee
Keyword(s):  
Cell Cycle ◽  
Transcriptional Regulation ◽  
Cell Cycle Control ◽  
Retinoblastoma Protein

On the importance of protein phosphorylation in cell cycle control

1993 ◽  
Vol 127-128 (1) ◽  
pp. 267-281 ◽  
Author(s):  
James L. Maller
Keyword(s):  
Cell Cycle ◽  
Protein Phosphorylation ◽  
Cell Cycle Control

scholarly journals Interchangeable Roles for E2F Transcriptional Repression by the Retinoblastoma Protein and p27KIP1–Cyclin-Dependent Kinase Regulation in Cell Cycle Control and Tumor Suppression

2016 ◽  
Vol 37 (2) ◽  
Author(s):  
Michael J. Thwaites ◽  
Matthew J. Cecchini ◽  
Daniel T. Passos ◽  
Ian Welch ◽  
Frederick A. Dick
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Transcriptional Repression ◽  
Cell Cycle Control ◽  
Retinoblastoma Protein ◽  
Level Control ◽  
Mutant Genotype ◽  
Single Mutant ◽  
Cdk Regulation

ABSTRACT The mammalian G1-S phase transition is controlled by the opposing forces of cyclin-dependent kinases (CDK) and the retinoblastoma protein (pRB). Here, we present evidence for systems-level control of cell cycle arrest by pRB-E2F and p27-CDK regulation. By introducing a point mutant allele of pRB that is defective for E2F repression (Rb1 G ) into a p27KIP1 null background (Cdkn1b −/−), both E2F transcriptional repression and CDK regulation are compromised. These double-mutant Rb1 G/G ; Cdkn1b −/− mice are viable and phenocopy Rb1 +/− mice in developing pituitary adenocarcinomas, even though neither single mutant strain is cancer prone. Combined loss of pRB-E2F transcriptional regulation and p27KIP1 leads to defective proliferative control in response to various types of DNA damage. In addition, Rb1 G/G ; Cdkn1b −/− fibroblasts immortalize faster in culture and more frequently than either single mutant genotype. Importantly, the synthetic DNA damage arrest defect caused by Rb1 G/G ; Cdkn1b −/− mutations is evident in the developing intermediate pituitary lobe where tumors ultimately arise. Our work identifies a unique relationship between pRB-E2F and p27-CDK control and offers in vivo evidence that pRB is capable of cell cycle control through E2F-independent effects.

scholarly journals The Retinoblastoma Protein Regulates Pericentric Heterochromatin

2006 ◽  
Vol 26 (9) ◽  
pp. 3659-3671 ◽  
Author(s):  
Christian E. Isaac ◽  
Sarah M. Francis ◽  
Alison L. Martens ◽  
Lisa M. Julian ◽  
Laurie A. Seifried ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Chromatin Structure ◽  
Cell Cycle Progression ◽  
Cell Cycle Control ◽  
Retinoblastoma Protein ◽  
Pericentric Heterochromatin ◽  
Site Mutation ◽  
Histone Tails ◽  
Binding Cleft ◽  
Heterochromatin Structure

ABSTRACT The retinoblastoma protein (pRb) has been proposed to regulate cell cycle progression in part through its ability to interact with enzymes that modify histone tails and create a repressed chromatin structure. We created a mutation in the murine Rb1 gene that disrupted pRb's ability to interact with these enzymes to determine if it affected cell cycle control. Here, we show that loss of this interaction slows progression through mitosis and causes aneuploidy. Our experiments reveal that while the LXCXE binding site mutation does not disrupt pRb's interaction with the Suv4-20h histone methyltransferases, it dramatically reduces H4-K20 trimethylation in pericentric heterochromatin. Disruption of heterochromatin structure in this chromosomal region leads to centromere fusions, chromosome missegregation, and genomic instability. These results demonstrate the surprising finding that pRb uses the LXCXE binding cleft to control chromatin structure for the regulation of events beyond the G1-to-S-phase transition.

scholarly journals Stabilization of the Retinoblastoma Protein by A-Type Nuclear Lamins Is Required for INK4A-Mediated Cell Cycle Arrest

2006 ◽  
Vol 26 (14) ◽  
pp. 5360-5372 ◽  
Author(s):  
Ryan T. Nitta ◽  
Samantha A. Jameson ◽  
Brian A. Kudlow ◽  
Lindus A. Conlan ◽  
Brian K. Kennedy
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Cell Cycle Arrest ◽  
Cell Cycle Control ◽  
Retinoblastoma Protein ◽  
Lamin A ◽  
Nuclear Lamins ◽  
Cycle Arrest ◽  
Functional Consequences ◽  
Mandibuloacral Dysplasia

ABSTRACT Mutations in the LMNA gene, which encodes all A-type lamins, including lamin A and lamin C, cause a variety of tissue-specific degenerative diseases termed laminopathies. Little is known about the pathogenesis of these disorders. Previous studies have indicated that A-type lamins interact with the retinoblastoma protein (pRB). Here we probe the functional consequences of this association and further examine links between nuclear structure and cell cycle control. Since pRB is required for cell cycle arrest by p16ink4a, we tested the responsiveness of multiple lamin A/C-depleted cell lines to overexpression of this CDK inhibitor and tumor suppressor. We find that the loss of A-type lamin expression results in marked destabilization of pRB. This reduction in pRB renders cells resistant to p16ink4a-mediated G1 arrest. Reintroduction of lamin A, lamin C, or pRB restores p16ink4a-responsiveness to Lmna −/− cells. An array of lamin A mutants, representing a variety of pathologies as well as lamin A processing mutants, was introduced into Lmna −/− cells. Of these, a mutant associated with mandibuloacral dysplasia (MAD R527H), as well as two lamin A processing mutants, but not other disease-associated mutants, failed to restore p16ink4a responsiveness. Although our findings do not rule out links between altered pRB function and laminopathies, they fail to support such an assertion. These findings do link lamin A/C to the functional activation of a critical tumor suppressor pathway and further the possibility that somatic mutations in LMNA contribute to tumor progression.

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