The Role of Retinoblastoma Protein in Cell Cycle Regulation: An Updated Review

2021 ◽  
Vol 20 ◽  
Author(s):  
Rabih Roufayel ◽  
Rabih Mezher ◽  
Kenneth B. Storey
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Transcription Factors ◽  
Cell Cycle Control ◽  
Expression Of Genes ◽  
E2f Transcription Factor ◽  
Cellular Energetics ◽  
Development And Differentiation ◽  
E2f Transcription Factors ◽  
Rb Phosphorylation

: Selected transcription factors have critical roles to play in organism survival by regulating the expression of genes that control the adaptations needed to handle stress conditions. The retinoblastoma (Rb) protein coupled with the E2F transcription factor family was demonstrated to have roles in controlling the cell cycle during freezing and associated environmental stresses (anoxia, dehydration). Rb phosphorylation or acetylation at different sites provide a mechanism for repressing cell proliferation that is under the control of E2F transcription factors in animals facing stresses that disrupt cellular energetics or cell volume controls. Other central regulators of the cell cycle including Cyclins, Cyclin dependent kinases (Cdks), and checkpoint proteins detect DNA damage or any improper replication, blocking further progression of cell cycle and interrupting cell proliferation. This review provides an insight into the molecular regulatory mechanisms of cell cycle control, focusing on Rb-E2F along with Cyclin-Cdk complexes typically involved in development and differentiation that need to be regulated in order to survive extreme cellular stress.

scholarly journals A role for the DP subunit of the E2F transcription factor in axis determination during Drosophila oogenesis

Development ◽  
2000 ◽  
Vol 127 (15) ◽  
pp. 3249-3261 ◽  
Author(s):  
D.L. Myster ◽  
P.C. Bonnette ◽  
R.J. Duronio
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Dna Replication ◽  
Cell Cycle Progression ◽  
Nurse Cell ◽  
Cell Cycle Control ◽  
Egg Chambers ◽  
E2f Transcription Factors ◽  
Mutant Phenotypes ◽  
Replication Factors

The E2F family of transcription factors contributes to cell cycle control by regulating the transcription of DNA replication factors. Functional ‘E2F’ is a DNA-binding heterodimer composed of E2F and DP proteins. Drosophila contains two E2F genes (dE2F, dE2F2) and one DP gene (dDP). Mutation of either dE2F or dDP eliminates G(1)-S transcription of known replication factors during embryogenesis and compromises DNA replication. However, the analysis of these mutant phenotypes is complicated by the perdurance of maternally supplied gene function. To address this and to further analyze the role of E2F transcription factors in development we have phenotypically characterized mitotic clones of dDP mutant cells in the female germline. Our analysis indicates that dDP is required for several essential processes during oogenesis. In a fraction of the mutant egg chambers the germ cells execute one extra round of mitosis, suggesting that in this tissue dDP is uniquely utilized for cell cycle arrest rather than cell cycle progression. Mutation of dDP in the germline also prevents nurse cell cytoplasm transfer to the oocyte, resulting in a ‘dumpless’ phenotype that blocks oocyte development. This phenotype likely results from both disruption of the actin cytoskeleton and a failure of nurse cell apoptosis, each of which are required for normal cytoplasmic transfer. Lastly, we found that dDP is required for the establishment of the dorsal-ventral axis, as loss of dDP function prevents the localized expression of the EGFR ligand Gurken in the oocyte, which initiates dorsal-ventral polarity in the egg chamber. Thus we have uncovered new functions for E2F transcription factors during development, including an unexpected role in pattern formation.

scholarly journals Plant D–type cyclins and the control of G1 progression

2002 ◽  
Vol 357 (1422) ◽  
pp. 749-760 ◽  
Author(s):  
E. Ann Oakenfull ◽  
Catherine Riou-Khamlichi ◽  
A. H. Murray
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
S Phase ◽  
G1 Phase ◽  
Basic Pattern ◽  
Rb Protein ◽  
E2f Transcription Factors ◽  
Rb Phosphorylation ◽  
Phase Entry ◽  
Plant Homologue

The basic pattern of controls that operate during the G1 phase of the plant cell cycle shows much closer similarity to animals than to the yeasts and other fungi. The activity of D–type cyclin (CycD) kinases is induced in response to stimulatory signals, and these phosphorylate the plant homologue of the retinoblastoma tumour susceptibility (Rb) protein. It is likely that Rb phosphorylation results in the activation of genes under the control of E2F transcription factors, including those required for S phase entry. As the initial triggers of the cascade, attention has focused on the CycDs, and a family of 10 genes is present in Arabidopsis , divided into three major and three minor groups. Analysis to date suggests that these groups are functionally distinct.

scholarly journals Phosphorylation of the RB C-terminus regulates condensin II release from chromatin

2020 ◽  
pp. jbc.RA120.016511
Author(s):  
Seung J Kim ◽  
James I MacDonald ◽  
Frederick A. Dick
Keyword(s):  
Cell Cycle ◽  
Genome Stability ◽  
Cell Cycle Control ◽  
Cell Receptor ◽  
Receptor Activation ◽  
Biologically Relevant ◽  
C Terminus ◽  
Independent Functions ◽  
Phosphorylation Event ◽  
Rb Phosphorylation

The retinoblastoma tumour suppressor protein (RB) plays an important role in biological processes such as cell cycle control, DNA damage repair, epigenetic regulation, and genome stability. The canonical model of RB regulation is that cyclin-CDKs phosphorylate, and render RB inactive in late G1/S, promoting entry into S phase. Recently, mono-phosphorylated RB species were described to have distinct cell-cycle independent functions, suggesting that a phosphorylation code dictates diversity of RB function. However, a biologically relevant, functional role of RB phosphorylation at non-CDK sites has remained elusive. Here, we investigated S838/T841 dual phosphorylation, its upstream stimulus, and downstream functional output.  We found that mimicking T-cell receptor activation in Jurkat leukemia cells induced sequential activation of downstream kinases including p38 MAPK, and RB S838/T841 phosphorylation.  This signaling pathway disrupts RB and condensin II interaction with chromatin.  Using cells expressing a WT or S838A/T841A mutant RB fragment, we present evidence that deficiency for this phosphorylation event prevents condensin II release from chromatin.

scholarly journals Cell-Cycle Control of Developmentally Regulated Transcription Factors Accounts for Heterogeneity in Human Pluripotent Cells

2013 ◽  
Vol 1 (6) ◽  
pp. 532-544 ◽  
Author(s):  
Amar M. Singh ◽  
James Chappell ◽  
Robert Trost ◽  
Li Lin ◽  
Tao Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Cell Cycle Control ◽  
Pluripotent Cells ◽  
Developmentally Regulated

scholarly journals MSH2 is required for cell proliferation, cell cycle control and cell invasiveness in colorectal cancer cells

2012 ◽  
Vol 57 (20) ◽  
pp. 2580-2585
Author(s):  
Kai Shen ◽  
YingJiang Ye ◽  
KeWei Jiang ◽  
Bin Liang ◽  
XiaoDong Yang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cell Cycle Control ◽  
Colorectal Cancer Cells ◽  
Cell Invasiveness

scholarly journals The transcription factors TFE3 and TFEB amplify p53 dependent transcriptional programs in response to DNA damage

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Eutteum Jeong ◽  
Owen A Brady ◽  
José A Martina ◽  
Mehdi Pirooznia ◽  
Ilker Tunc ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Transcription Factors ◽  
P53 Protein ◽  
Cell Cycle Control ◽  
Cell Cycle Checkpoints ◽  
Dependent Manner ◽  
Double Knockout ◽  
Protein Levels ◽  
Regulation Of Cell Cycle

The transcription factors TFE3 and TFEB cooperate to regulate autophagy induction and lysosome biogenesis in response to starvation. Here we demonstrate that DNA damage activates TFE3 and TFEB in a p53 and mTORC1 dependent manner. RNA-Seq analysis of TFEB/TFE3 double-knockout cells exposed to etoposide reveals a profound dysregulation of the DNA damage response, including upstream regulators and downstream p53 targets. TFE3 and TFEB contribute to sustain p53-dependent response by stabilizing p53 protein levels. In TFEB/TFE3 DKOs, p53 half-life is significantly decreased due to elevated Mdm2 levels. Transcriptional profiles of genes involved in lysosome membrane permeabilization and cell death pathways are dysregulated in TFEB/TFE3-depleted cells. Consequently, prolonged DNA damage results in impaired LMP and apoptosis induction. Finally, expression of multiple genes implicated in cell cycle control is altered in TFEB/TFE3 DKOs, revealing a previously unrecognized role of TFEB and TFE3 in the regulation of cell cycle checkpoints in response to stress.

Abnormalities in Cell Cycle Control in Cancer and Their Clinical Implications

1998 ◽  
Vol 84 (4) ◽  
pp. 421-433 ◽  
Author(s):  
Alessandro Sgambato ◽  
Giovanna Flamini ◽  
Achille Cittadini ◽  
I. Bernard Weinstein
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Transformation ◽  
Cell Cycle Control ◽  
Genomic Stability ◽  
Clinical Implications ◽  
Mammalian Cell Cycle ◽  
Carcinogenic Process ◽  
Review Current

Recent studies indicate that the functions of several genes that control the cell cycle are altered during the carcinogenic process and that these changes perturb both cell proliferation and genomic stability, thus promoting cell transformation and enhancing the process of tumor progression. The purpose of this paper is to review current information on the role of cyclins and related genes in the control of the mammalian cell cycle, the types of abnormalities in these genes found in human tumors and the possible clinical implications of these findings.

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