scholarly journals Histone Deacetylase 3 Regulates Cyclin A Stability

2013 ◽  
Vol 288 (29) ◽  
pp. 21096-21104 ◽  
Author(s):  
Miriam Vidal-Laliena ◽  
Edurne Gallastegui ◽  
Francesca Mateo ◽  
Marian Martínez-Balbás ◽  
Maria Jesús Pujol ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Histone Deacetylase ◽  
Cell Cycle Progression ◽  
Proteasome Inhibitors ◽  
Cyclin A ◽  
S Phase ◽  
Cycle Progression ◽  
Histone Deacetylase 3 ◽  
Lysine Residues ◽  
Phase Progression

PCAF and GCN5 acetylate cyclin A at specific lysine residues targeting it for degradation at mitosis. We report here that histone deacetylase 3 (HDAC3) directly interacts with and deacetylates cyclin A. HDAC3 interacts with a domain included in the first 171 aa of cyclin A, a region involved in the regulation of its stability. In cells, overexpression of HDAC3 reduced cyclin A acetylation whereas the knocking down of HDAC3 increased its acetylation. Moreover, reduction of HDAC3 levels induced a decrease of cyclin A that can be reversed by proteasome inhibitors. These results indicate that HDAC3 is able to regulate cyclin A degradation during mitosis via proteasome. Interestingly, HDAC3 is abruptly degraded at mitosis also via proteasome thus facilitating cyclin A acetylation by PCAF/GCN5, which will target cyclin A for degradation. Because cyclin A is crucial for S phase progression and mitosis entry, the knock down of HDAC3 affects cell cycle progression specifically at both, S phase and G2/M transition. In summary we propose here that HDAC3 regulates cyclin A stability by counteracting the action of the acetylases PCAF/GCN5.

scholarly journals The Meiosis-Specific Crs1 Cyclin Is Required for Efficient S-Phase Progression and Stable Nuclear Architecture

2021 ◽  
Vol 22 (11) ◽  
pp. 5483
Author(s):  
Luisa F. Bustamante-Jaramillo ◽  
Celia Ramos ◽  
Cristina Martín-Castellanos
Keyword(s):  
Cell Cycle ◽  
Translational Control ◽  
Cell Cycle Progression ◽  
Nuclear Architecture ◽  
Strand Break ◽  
Spindle Pole ◽  
S Phase ◽  
Cycle Progression ◽  
Single Wave ◽  
Phase Progression

Cyclins and CDKs (Cyclin Dependent Kinases) are key players in the biology of eukaryotic cells, representing hubs for the orchestration of physiological conditions with cell cycle progression. Furthermore, as in the case of meiosis, cyclins and CDKs have acquired novel functions unrelated to this primal role in driving the division cycle. Meiosis is a specialized developmental program that ensures proper propagation of the genetic information to the next generation by the production of gametes with accurate chromosome content, and meiosis-specific cyclins are widespread in evolution. We have explored the diversification of CDK functions studying the meiosis-specific Crs1 cyclin in fission yeast. In addition to the reported role in DSB (Double Strand Break) formation, this cyclin is required for meiotic S-phase progression, a canonical role, and to maintain the architecture of the meiotic chromosomes. Crs1 localizes at the SPB (Spindle Pole Body) and is required to stabilize the cluster of telomeres at this location (bouquet configuration), as well as for normal SPB motion. In addition, Crs1 exhibits CDK(Cdc2)-dependent kinase activity in a biphasic manner during meiosis, in contrast to a single wave of protein expression, suggesting a post-translational control of its activity. Thus, Crs1 displays multiple functions, acting both in cell cycle progression and in several key meiosis-specific events.

scholarly journals Cell Cycle Dysregulation by Human Cytomegalovirus: Influence of the Cell Cycle Phase at the Time of Infection and Effects on Cyclin Transcription

1998 ◽  
Vol 72 (5) ◽  
pp. 3729-3741 ◽  
Author(s):  
Bryan S. Salvant ◽  
Elizabeth A. Fortunato ◽  
Deborah H. Spector
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Cell Cycle Progression ◽  
Hcmv Infection ◽  
Cyclin A ◽  
S Phase ◽  
Cyclin B ◽  
Cycle Progression ◽  
Cycle Arrest ◽  
Time Of Infection

ABSTRACT Human cytomegalovirus (HCMV) infection inhibits cell cycle progression and alters the expression of cyclins E, A, and B (F. M. Jault, J.-M. Jault, F. Ruchti, E. A. Fortunato, C. Clark, J. Corbeil, D. D. Richman, and D. H. Spector, J. Virol. 69:6697–6704, 1995). In this study, we examined cell cycle progression, cyclin gene expression, and early viral events when the infection was initiated at different points in the cell cycle (G0, G1, and S). In all cases, infection led to cell cycle arrest. Cells infected in G0 or G1phase also showed a complete or partial absence, respectively, of cellular DNA synthesis at a time when DNA synthesis occurred in the corresponding mock-infected cells. In contrast, when cells were infected near or during S phase, many cells were able to pass through S phase and undergo mitosis prior to cell cycle arrest. S-phase infection also produced a delay in the appearance of the viral cytopathic effect and in the synthesis of immediate-early and early proteins. Labeling of cells with bromodeoxyuridine immediately prior to HCMV infection in S phase revealed that viral protein expression occurred primarily in cells which were not engaged in DNA synthesis at the time of infection. The viral-mediated induction of cyclin E, maintenance of cyclin-B protein levels, and inhibitory effects on the accumulation of cyclin A were not significantly affected when infection occurred during different phases of the cell cycle (G0, G1, and S). However, there was a delay in the observed inhibition of cyclin A in cells infected during S phase. This finding was in accord with the pattern of cell cycle progression and delay in viral gene expression associated with S-phase infection. Analysis of the mRNA revealed that the effects of the virus on cyclin E and cyclin A, but not on cyclin B, were primarily at the transcriptional level.

scholarly journals A Protein Encoded by the Latency-Related Gene of Bovine Herpesvirus 1 Is Expressed in Trigeminal Ganglionic Neurons of Latently Infected Cattle and Interacts with Cyclin-Dependent Kinase 2 during Productive Infection

1998 ◽  
Vol 72 (10) ◽  
pp. 8133-8142 ◽  
Author(s):  
Yunquan Jiang ◽  
Ashfaque Hossain ◽  
Maria Teresa Winkler ◽  
Todd Holt ◽  
Alan Doster ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Acute Infection ◽  
Cyclin A ◽  
S Phase ◽  
Cyclin Dependent Kinase ◽  
Bovine Herpesvirus 1 ◽  
Cycle Progression ◽  
Latently Infected ◽  
Herpesvirus 1

ABSTRACT Despite productive viral gene expression in the peripheral nervous system during acute infection, the bovine herpesvirus 1 (BHV-1) infection cycle is blocked in sensory ganglionic neurons and consequently latency is established. The only abundant viral transcript expressed during latency is the latency-related (LR) RNA. LR gene products inhibit S-phase entry, and binding of the LR protein (LRP) to cyclin A was hypothesized to block cell cycle progression. This study demonstrates LRP is a nuclear protein which is expressed in neurons of latently infected cattle. Affinity chromatography indicated that LRP interacts with cyclin-dependent kinase 2 (cdk2)-cyclin complexes or cdc2-cyclin complexes in transfected human cells or infected bovine cells. After partial purification using three different columns (DEAE-Sepharose, Econo S, and heparin-agarose), LRP was primarily associated with cdk2-cyclin E complexes, an enzyme which is necessary for G1-to-S-phase cell cycle progression. During acute infection of trigeminal ganglia or following dexamethasone-induced reactivation, BHV-1 induces expression of cyclin A in neurons (L. M. Schang, A. Hossain, and C. Jones, J. Virol. 70:3807–3814, 1996). Expression of S-phase regulatory proteins (cyclin A, for example) leads to neuronal apoptosis. Consequently, we hypothesize that interactions between LRP and cell cycle regulatory proteins promote survival of postmitotic neurons during acute infection and/or reactivation.

scholarly journals p50 mono-ubiquitination and interaction with BARD1 regulates cell cycle progression and maintains genome stability

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Longtao Wu ◽  
Clayton D. Crawley ◽  
Andrea Garofalo ◽  
Jackie W. Nichols ◽  
Paige-Ashley Campbell ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Genome Stability ◽  
Cell Cycle Progression ◽  
Human Cancer ◽  
S Phase ◽  
Post Translational Modification ◽  
Chromosomal Breakage ◽  
Cycle Progression ◽  
Genome Wide ◽  
Phase Progression

Abstract p50, the mature product of NFKB1, is constitutively produced from its precursor, p105. Here, we identify BARD1 as a p50-interacting factor. p50 directly associates with the BARD1 BRCT domains via a C-terminal phospho-serine motif. This interaction is induced by ATR and results in mono-ubiquitination of p50 by the BARD1/BRCA1 complex. During the cell cycle, p50 is mono-ubiquitinated in S phase and loss of this post-translational modification increases S phase progression and chromosomal breakage. Genome-wide studies reveal a substantial decrease in p50 chromatin enrichment in S phase and Cycln E is identified as a factor regulated by p50 during the G1 to S transition. Functionally, interaction with BARD1 promotes p50 protein stability and consistent with this, in human cancer specimens, low nuclear BARD1 protein strongly correlates with low nuclear p50. These data indicate that p50 mono-ubiquitination by BARD1/BRCA1 during the cell cycle regulates S phase progression to maintain genome integrity.

scholarly journals Multiple Functions of Fubp1 in Cell Cycle Progression and Cell Survival

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1347 ◽  
Author(s):  
Mingyu Kang ◽  
Hyeon Ji Kim ◽  
Tae-Jun Kim ◽  
Jin-Seok Byun ◽  
Jae-Ho Lee ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Metabolic Stress ◽  
Cyclin A ◽  
S Phase ◽  
Cycle Progression ◽  
Genes Encoding ◽  
Double Agent

The discovery of novel and critical genes implicated in malignant development is a topic of high interest in cancer research. Intriguingly, a group of genes named “double-agent” genes were reported to have both oncogenic and tumor-suppressive functions. To date, less than 100 “double-agent” genes have been documented. Fubp1 is a master transcriptional regulator of a subset of genes by interacting with a far upstream element (FUSE). Mounting evidence has collectively demonstrated both the oncogenic and tumor suppressive roles of Fubp1 and the debate regarding its roles in tumorigenesis has been around for several years. Therefore, the detailed molecular mechanisms of Fubp1 need to be determined in each context. In the present study, we showed that the Fubp1 protein level was enriched in the S phase and we identified that Fubp1 deficiency altered cell cycle progression, especially in the S phase, by downregulating the mRNA expression levels of Ccna genes encoding cyclin A. Although this Fubp1-cyclin A axis appears to exist in several types of tumors, Fubp1 showed heterogeneous expression patterns among various cancer tissues, suggesting it exhibits multiple and complicated functions in cancer development. In addition, we showed that Fubp1 deficiency confers survival advantages to cells against metabolic stress and anti-cancer drugs, suggesting that Fubp1 may play both positive and negative roles in malignant development.

scholarly journals Regulation of Late G1/S Phase Transition and APCCdh1 by Reactive Oxygen Species

2006 ◽  
Vol 26 (12) ◽  
pp. 4701-4711 ◽  
Author(s):  
Courtney G. Havens ◽  
Alan Ho ◽  
Naohisa Yoshioka ◽  
Steven F. Dowdy
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Cell Size ◽  
Cell Cycle Progression ◽  
Reactive Oxygen ◽  
Cyclin A ◽  
S Phase ◽  
Oxygen Species ◽  
Cycle Progression ◽  
Mitochondrial Mass

ABSTRACT Proliferating cells have a higher metabolic rate than quiescent cells. To investigate the role of metabolism in cell cycle progression, we examined cell size, mitochondrial mass, and reactive oxygen species (ROS) levels in highly synchronized cell populations progressing from early G1 to S phase. We found that ROS steadily increased, compared to cell size and mitochondrial mass, through the cell cycle. Since ROS has been shown to influence cell proliferation and transformation, we hypothesized that ROS could contribute to cell cycle progression. Antioxidant treatment of cells induced a late-G1-phase cell cycle arrest characterized by continued cellular growth, active cyclin D-Cdk4/6 and active cyclin E-Cdk2 kinases, and inactive hyperphosphorylated pRb. However, antioxidant-treated cells failed to accumulate cyclin A protein, a requisite step for initiation of DNA synthesis. Further examination revealed that cyclin A continued to be ubiquitinated by the anaphase promoting complex (APC) and to be degraded by the proteasome. This antioxidant arrest could be rescued by overexpression of Emi1, an APC inhibitor. These observations reveal an intrinsic late-G1-phase checkpoint, after transition across the growth factor-dependent G1 restriction point, that links increased steady-state levels of endogenous ROS and cell cycle progression through continued activity of APC in association with Cdh1.

scholarly journals The Stress-activated Protein Kinase Hog1 Mediates S Phase Delay in Response to Osmostress

2009 ◽  
Vol 20 (15) ◽  
pp. 3572-3582 ◽  
Author(s):  
Gilad Yaakov ◽  
Alba Duch ◽  
María García-Rubio ◽  
Josep Clotet ◽  
Javier Jimenez ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Activity ◽  
S Phase ◽  
Cyclin Dependent Kinase ◽  
Cycle Progression ◽  
Replication Complex ◽  
Extracellular Stimuli ◽  
Phase Progression ◽  
Cell Cycle Machinery

Control of cell cycle progression by stress-activated protein kinases (SAPKs) is essential for cell adaptation to extracellular stimuli. Exposure of yeast to osmostress activates the Hog1 SAPK, which modulates cell cycle progression at G1 and G2 by the phosphorylation of elements of the cell cycle machinery, such as Sic1 and Hsl1, and by down-regulation of G1 and G2 cyclins. Here, we show that upon stress, Hog1 also modulates S phase progression. The control of S phase is independent of the S phase DNA damage checkpoint and of the previously characterized Hog1 cell cycle targets Sic1 and Hsl1. Hog1 uses at least two distinct mechanisms in its control over S phase progression. At early S phase, the SAPK prevents firing of replication origins by delaying the accumulation of the S phase cyclins Clb5 and Clb6. In addition, Hog1 prevents S phase progression when activated later in S phase or cells containing a genetic bypass for cyclin-dependent kinase activity. Hog1 interacts with components of the replication complex and delays phosphorylation of the Dpb2 subunit of the DNA polymerase. The two mechanisms of Hog1 action lead to delayed firing of origins and prolonged replication, respectively. The Hog1-dependent delay of replication could be important to allow Hog1 to induce gene expression before replication.

scholarly journals SAMHD1 Phosphorylation at T592 Regulates Cellular Localization and S-phase Progression

2021 ◽  
Vol 8 ◽  
Author(s):  
Stephanie Batalis ◽  
LeAnn C. Rogers ◽  
Wayne O. Hemphill ◽  
Christopher H. Mauney ◽  
David A. Ornelles ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Nuclear Localization ◽  
Cellular Localization ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Oxygen Species ◽  
Wild Type ◽  
Cycle Progression ◽  
Catalytically Active ◽  
Phase Progression

SAMHD1 activity is regulated by a network of mechanisms including phosphorylation, oxidation, oligomerization, and others. Significant questions remain about the effects of phosphorylation on SAMHD1 function and activity. We investigated the effects of a SAMHD1 T592E phosphorylation mimic on its cellular localization, catalytic activity, and cell cycle progression. We found that the SAMHD1 T592E is a catalytically active enzyme that is inhibited by protein oxidation. SAMHD1 T592E is retained in the nucleus at higher levels than the wild-type protein during growth factor-mediated signaling. This nuclear localization protects SAMHD1 from oxidation by cytoplasmic reactive oxygen species. The SAMHD1 T592E phosphomimetic further inhibits the cell cycle S/G2 transition. This has significant implications for SAMHD1 function in regulating innate immunity, antiviral response and DNA replication.

scholarly journals Rad53 is essential for a mitochondrial DNA inheritance checkpoint regulating G1 to S progression

2012 ◽  
Vol 198 (5) ◽  
pp. 793-798 ◽  
Author(s):  
David G. Crider ◽  
Luis J. García-Rodríguez ◽  
Pallavi Srivastava ◽  
Leonardo Peraza-Reyes ◽  
Krishna Upadhyaya ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Mitochondrial Dna ◽  
Cell Cycle Progression ◽  
Dna Helicase ◽  
S Phase ◽  
Noncoding Dna ◽  
Cycle Progression ◽  
Checkpoint Pathway ◽  
Oxidase Inhibition ◽  
Phase Progression

The Chk2-mediated deoxyribonucleic acid (DNA) damage checkpoint pathway is important for mitochondrial DNA (mtDNA) maintenance. We show in this paper that mtDNA itself affects cell cycle progression. Saccharomyces cerevisiae rho0 cells, which lack mtDNA, were defective in G1- to S-phase progression. Deletion of subunit Va of cytochrome c oxidase, inhibition of F1F0 adenosine triphosphatase, or replacement of all mtDNA-encoded genes with noncoding DNA did not affect G1- to S-phase progression. Thus, the cell cycle progression defect in rho0 cells is caused by loss of DNA within mitochondria and not loss of respiratory activity or mtDNA-encoded genes. Rad53p, the yeast Chk2 homologue, was required for inhibition of G1- to S-phase progression in rho0 cells. Pif1p, a DNA helicase and Rad53p target, underwent Rad53p-dependent phosphorylation in rho0 cells. Thus, loss of mtDNA activated an established checkpoint kinase that inhibited G1- to S-phase progression. These findings support the existence of a Rad53p-regulated checkpoint that regulates G1- to S-phase progression in response to loss of mtDNA.

Polyamine dependence of normal cell-cycle progression

2003 ◽  
Vol 31 (2) ◽  
pp. 366-370 ◽  
Author(s):  
S.M. Oredsson
Keyword(s):  
Cell Cycle ◽  
Enzyme Activities ◽  
Cell Cycle Progression ◽  
Cyclin A ◽  
S Phase ◽  
Cycle Phase ◽  
Polyamine Biosynthesis ◽  
Cycle Progression ◽  
Elongation Step ◽  
Key Steps

The driving force of the cell cycle is the activities of cyclin-dependent kinases (CDKs). Key steps in the regulation of the cell cycle therefore must impinge upon the activities of the CDKs. CDKs exert their functions when bound to cyclins that are expressed cyclically during the cell cycle. Polyamine biosynthesis varies bicyclically during the cell cycle with peaks in enzyme activities at the G1/S and S/G2 transitions. The enzyme activities are regulated at transcriptional, translational and post-translational levels. When cells are seeded in the presence of drugs that interfere with polyamine biosynthesis, cell cycle progression is affected within one cell cycle after seeding. The cell cycle phase that is most sensitive to polyamine biosynthesis inhibition is the S phase, while effects on the G1 and G2/M phases occur at later time points. The elongation step of DNA replication is negatively affected when polyamine pools are not allowed to increase normally during cell proliferation. Cyclin A is expressed during the S phase and cyclin A/CDK2 is important for a normal rate of DNA elongation. Cyclin A expression is lowered in cells treated with polyamine biosynthesis inhibitors. Thus, polyamines may affect S phase progression by participating in the regulation of cyclin A expression.

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