The Mechanism of Retinoblastoma Protein-Mediated Terminal Cell Cycle Arrest

2003 ◽  
Author(s):  
Hasan N. Rajabi
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Retinoblastoma Protein ◽  
Terminal Cell ◽  
Cycle Arrest

scholarly journals Key role for p27Kip1, retinoblastoma protein Rb, and MYCN in polyamine inhibitor-induced G1 cell cycle arrest in MYCN-amplified human neuroblastoma cells

Oncogene ◽  
2005 ◽  
Vol 24 (36) ◽  
pp. 5606-5618 ◽  
Author(s):  
Christopher J Wallick ◽  
Ivonne Gamper ◽  
Mike Thorne ◽  
David J Feith ◽  
Kelsie Y Takasaki ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Neuroblastoma Cells ◽  
Retinoblastoma Protein ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest

The retinoblastoma protein and BRG1 form a complex and cooperate to induce cell cycle arrest

Cell ◽  
1994 ◽  
Vol 79 (1) ◽  
pp. 119-130 ◽  
Author(s):  
Joshua L. Dunaief ◽  
Bruce E. Strober ◽  
Sushovan Guha ◽  
Paul A. Khavari ◽  
Kimona Ålin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Retinoblastoma Protein ◽  
Induce Cell Cycle Arrest ◽  
Cycle Arrest

scholarly journals A potent transrepression domain in the retinoblastoma protein induces a cell cycle arrest when bound to E2F sites.

1995 ◽  
Vol 92 (25) ◽  
pp. 11544-11548 ◽  
Author(s):  
W. R. Sellers ◽  
J. W. Rodgers ◽  
W. G. Kaelin
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Retinoblastoma Protein ◽  
Cycle Arrest ◽  
A Cell

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.

scholarly journals Requirement for p27KIP1 in Retinoblastoma Protein-Mediated Senescence

2001 ◽  
Vol 21 (11) ◽  
pp. 3616-3631 ◽  
Author(s):  
Kamilah Alexander ◽  
Philip W. Hinds
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Kinase Activity ◽  
Kinase Inhibitor ◽  
Cyclin E ◽  
Ectopic Expression ◽  
Retinoblastoma Protein ◽  
Morphological Transformation ◽  
Cycle Arrest

ABSTRACT In vivo and in vitro evidence indicate that cells do not divide indefinitely but instead stop growing and undergo a process termed cellular proliferative senescence. Very little is known about how senescence occurs, but there are several indications that the retinoblastoma protein (pRb) is involved, the most striking being that reintroduction of RB into RB −/−tumor cell lines induces senescence. In investigating the mechanism by which pRb induces senescence, we have found that pRb causes a posttranscriptional accumulation of the cyclin-dependent kinase inhibitor p27KIP1 that is accompanied by an increase in p27KIP1 specifically bound to cyclin E and a concomitant decrease in cyclin E-associated kinase activity. In contrast, pRb-related proteins p107 and p130, which also decrease cyclin E-kinase activity, do not cause an accumulation of p27KIP1 and induce senescence poorly. In addition, the use of pRb proteins mutated in the pocket domain demonstrates that pRb upregulation of p27KIP1 and senescence induction do not require the interaction of pRb with E2F. Furthermore, ectopic expression of p21CIP1 or p27KIP1 induces senescence but not the morphology change associated with pRb-mediated senescence, uncoupling senescence from the morphological transformation. Finally, the ability of pRb to maintain cell cycle arrest and induce senescence is reversibly abrogated by ablation of p27KIP1 expression. These findings suggest that prolonged cell cycle arrest through the persistent and specific inhibition of cdk2 activity by p27KIP1 is critical for pRb-induced senescence.

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