scholarly journals A bHLH-PAS protein regulates light-dependent diurnal rhythmic processes in the marine diatomPhaeodactylum tricornutum

2018 ◽  
Author(s):  
Rossella Annunziata ◽  
Andrés Ritter ◽  
Antonio Emidio Fortunato ◽  
Soizic Cheminant-Navarro ◽  
Nicolas Agier ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Division ◽  
Cell Cycle Progression ◽  
Marine Diatom ◽  
Diurnal Rhythms ◽  
Biological Processes ◽  
Wild Type ◽  
Continuous Darkness ◽  
Altered Cell

ABSTRACTPeriodic light-dark cycles govern the timing of basic biological processes in organisms inhabiting land as well as the sea, where life evolved. Although prominent marine phytoplanktonic organisms such as diatoms show robust diurnal rhythms in growth, cell cycle and gene expression, the molecular foundations controlling these processes are still obscure. By exploring the regulatory landscape of diatom diurnal rhythms, we unveil the function of aPhaeodactylum tricornutumbHLH-PAS protein,PtbHLH1a, in the regulation of light-dependent diurnal rhythms. Peak expression ofPtbHLH1amRNA occurs toward the end of the light period and it adjusts to photoperiod changes. Ectopic over-expression ofPtbHLH1a results in lines showing a phase shift in diurnal cell fluorescence, compared to the wild-type cells, and with altered cell cycle progression and gene expression. Reduced oscillations in gene expression are also observed in overexpression lines compared to wild-type in continuous darkness, showing that the regulation of rhythmicity byPtbHLH1a is not directly dependent on light inputs and cell division.PtbHLH1a homologs are widespread in diatom genomes which may indicate a common function in many species. This study adds new elements to understand diatom biology and ecology and offers new perspectives to elucidate timekeeping mechanisms in marine organisms belonging to a major, but underinvestigated branch of the tree of life.SIGNIFICANCE STATEMENTMost organisms experience diurnal light-dark changes and show rhythms of basic biological processes such that they occur at optimal times of the day. The ocean harbours a huge diversity of organisms showing light-dependent rhythms, but their molecular foundations are still largely unknown. In this study, we discover a novel protein,PtbHLH1a that regulates cell division, gene expression and the diurnal timing of these events in the marine diatomPhaedoactylum tricornutum. The identification ofPtbHLH1a-like genes in many diatom species suggests a conserved function in diurnal rhythm regulation in the most species-rich group of algae in the ocean. This study unveils critical features of diatom biology and advances the field of marine rhythms and their environmental regulation.

scholarly journals Inhibition of Cell Division by the Human Cytomegalovirus IE86 Protein: Role of the p53 Pathway or Cyclin-Dependent Kinase 1/Cyclin B1

2005 ◽  
Vol 79 (4) ◽  
pp. 2597-2603 ◽  
Author(s):  
Yoon-Jae Song ◽  
Mark F. Stinski
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Human Cytomegalovirus ◽  
Cell Cycle Progression ◽  
Fibroblast Cell ◽  
Cyclin B1 ◽  
S Phase ◽  
Cyclin Dependent Kinase ◽  
Wild Type ◽  
Atm Kinase

ABSTRACT The human cytomegalovirus (HCMV) IE86 protein induces the human fibroblast cell cycle from G0/G1 to G1/S, where cell cycle progression stops. Cells with a wild-type, mutated, or null p53 or cells with null p21 protein were transduced with replication-deficient adenoviruses expressing HCMV IE86 protein or cellular p53 or p21. Even though S-phase genes were activated in a p53 wild-type cell, IE86 protein also induced phospho-Ser15 p53 and p21 independent of p14ARF but dependent on ATM kinase. These cells did not enter the S phase. In human p53 mutant, p53 null, or p21 null cells, IE86 protein did not up-regulate p21, cellular DNA synthesis was not inhibited, but cell division was inhibited. Cells accumulated in the G2/M phase, and there was increased cyclin-dependent kinase 1/cyclin B1 activity. Although the HCMV IE86 protein increases cellular E2F activity, it also blocks cell division in both p53+/+ and p53−/− cells.

scholarly journals Cardiac myosin binding protein C regulates postnatal myocyte cytokinesis

2015 ◽  
Vol 112 (29) ◽  
pp. 9046-9051 ◽  
Author(s):  
Jianming Jiang ◽  
Patrick G. Burgon ◽  
Hiroko Wakimoto ◽  
Kenji Onoue ◽  
Joshua M. Gorham ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Protein C ◽  
Cell Cycle Progression ◽  
Cardiac Myosin ◽  
Wild Type ◽  
Cycle Progression ◽  
Myosin Binding Protein ◽  
Myosin Binding Protein C ◽  
Myosin Binding

Homozygous cardiac myosin binding protein C-deficient (Mybpct/t) mice develop dramatic cardiac dilation shortly after birth; heart size increases almost twofold. We have investigated the mechanism of cardiac enlargement in these hearts. Throughout embryogenesis myocytes undergo cell division while maintaining the capacity to pump blood by rapidly disassembling and reforming myofibrillar components of the sarcomere throughout cell cycle progression. Shortly after birth, myocyte cell division ceases. Cardiac MYBPC is a thick filament protein that regulates sarcomere organization and rigidity. We demonstrate that many Mybpct/t myocytes undergo an additional round of cell division within 10 d postbirth compared with their wild-type counterparts, leading to increased numbers of mononuclear myocytes. Short-hairpin RNA knockdown of Mybpc3 mRNA in wild-type mice similarly extended the postnatal window of myocyte proliferation. However, adult Mybpct/t myocytes are unable to fully regenerate the myocardium after injury. MYBPC has unexpected inhibitory functions during postnatal myocyte cytokinesis and cell cycle progression. We suggest that human patients with homozygous MYBPC3-null mutations develop dilated cardiomyopathy, coupled with myocyte hyperplasia (increased cell number), as observed in Mybpct/t mice. Human patients, with heterozygous truncating MYBPC3 mutations, like mice with similar mutations, have hypertrophic cardiomyopathy. However, the mechanism leading to hypertrophic cardiomyopathy in heterozygous MYBPC3+/− individuals is myocyte hypertrophy (increased cell size), whereas the mechanism leading to cardiac dilation in homozygous Mybpc3−/− mice is primarily myocyte hyperplasia.

scholarly journals bHLH-PAS protein RITMO1 regulates diel biological rhythms in the marine diatomPhaeodactylum tricornutum

2019 ◽  
Vol 116 (26) ◽  
pp. 13137-13142 ◽  
Author(s):  
Rossella Annunziata ◽  
Andrés Ritter ◽  
Antonio Emidio Fortunato ◽  
Alessandro Manzotti ◽  
Soizic Cheminant-Navarro ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Continuous Light ◽  
Biological Rhythms ◽  
Wide Distribution ◽  
Diurnal Rhythms ◽  
Wild Type ◽  
Continuous Darkness ◽  
Shed Light

Periodic light–dark cycles govern the timing of basic biological processes in organisms inhabiting land as well as the sea, where life evolved. Although prominent marine phytoplanktonic organisms such as diatoms show robust diel rhythms, the mechanisms regulating these processes are still obscure. By characterizing aPhaeodactylum tricornutumbHLH-PAS nuclear protein, hereby named RITMO1, we shed light on the regulation of the daily life of diatoms. Alteration of RITMO1 expression levels and timing by ectopic overexpression results in lines with deregulated diurnal gene expression profiles compared with the wild-type cells. Reduced gene expression oscillations are also observed in these lines in continuous darkness, showing that the regulation of rhythmicity by RITMO1 is not directly dependent on light inputs. We also describe strong diurnal rhythms of cellular fluorescence in wild-type cells, which persist in continuous light conditions, indicating the existence of an endogenous circadian clock in diatoms. The altered rhythmicity observed in RITMO1 overexpression lines in continuous light supports the involvement of this protein in circadian rhythm regulation. Phylogenetic analysis reveals a wide distribution of RITMO1-like proteins in the genomes of diatoms as well as in other marine algae, which may indicate a common function in these phototrophs. This study adds elements to our understanding of diatom biology and offers perspectives to elucidate timekeeping mechanisms in marine organisms belonging to a major, but under-investigated, branch of the tree of life.

ID3 Is a Novel Tumor Suppressor Gene in Burkitt Lymphom

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 898-898
Author(s):  
Cassandra L Love ◽  
Dereje Jima ◽  
Zhen Sun ◽  
Rodney R. Miles ◽  
Cherie H. Dunphy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Tumor Suppressor ◽  
Burkitt Lymphoma ◽  
Cell Cycle Progression ◽  
Suppressor Gene ◽  
S Phase ◽  
Wild Type ◽  
Cycle Progression ◽  
Helix Loop Helix

Abstract Abstract 898 Burkitt Lymphoma (BL) is a highly proliferative form of non-Hodgkin lymphoma and is characterized by translocation of the C-MYC gene to the immunoglobulin gene loci resulting in deregulation. The role of collaborating gene mutations in BL is largely unknown. We performed whole exome sequencing and gene expression profiling of 57 Burkitt lymphoma and 94 DLBCL exomes. Mutational analysis revealed that ID3 is recurrently mutated in 38% of Burkitt lymphoma samples. ID3 mutations did not occur in any of the 94 DLBCL cases. ID3 gene expression was also found to be a distinguishing feature of Burkitt lymphomas (P<10−6), compared to DLBCL. We found a total of 27 distinct mutations in the ID3 genes among the 22 BL cases. These included five frameshift, four nonsense, and 18 missense mutations. We validated 16 of these events with Sanger sequencing with over 90% concordance. All of these mutations were located in the highly conserved helix-loop-helix region located on Exon 1. We explored the biological significance of ID3 mutations by initially comparing the gene expression profiles of BL cases that had mutated and wild-type ID3. Gene set enrichment analysis showed that those samples with mutated ID3 had higher expression of genes that were involved in cell cycle regulation, specifically those involved in the G1-S transition (P=0.01). In order to experimentally investigate the functional consequences of ID3 mutation, we generated mutant constructs corresponding to six different ID3 mutations observed in BLs. These mutant constructs were cloned into lentiviral vectors and overexpressed in BL cells that were wild type for ID3. We then performed cell cycle analysis for these wild type cells expressing GFP controls or the mutant constructs. We found that BL cells expressing each of the six mutant constructs demonstrated significant cell cycle progression from G1 to S phase compared to wild-type (P=0.01). Separately, we tested the effects of expressing mutant ID3 in cell proliferation assays and found that cells expressing mutant ID3 were considerably more proliferative than those expressing wild type (P=0.03). Conversely, we over-expressed the wild type form of ID3 in BL cells that had mutated ID3. These experiments completely rescued the observed phenotypes of the mutant ID3 constructs, with reduced cell cycle progression through increased G1 phase and decreased S-phase (P=0.04). We also noted decreased cell proliferation in these cells (P=0.03). These experiments support a role for ID3 as a novel tumor suppressor gene in Burkitt lymphoma. ID3 is a basic helix loop helix (bHLH) protein that binds to other E-proteins, blocking their ability to bind DNA. ID3 has been shown to be involved in a variety of biological processes including development and T and B cell differentiation. ID3 knockout mice have been shown to develop T cell as well as B cell lymphomas. Our data implicates this gene for the first time as a tumor suppressor in human cancer. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Control functions of adenovirus transformation region E1A gene products in rat and human cells.

1985 ◽  
Vol 5 (8) ◽  
pp. 1933-1939 ◽  
Author(s):  
A J Bellett ◽  
P Li ◽  
E T David ◽  
E J Mackey ◽  
A W Braithwaite ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cell Cycle Control ◽  
Viral Gene Expression ◽  
Human Cells ◽  
Early Gene ◽  
Wild Type Virus ◽  
Viral Gene ◽  
Altered Cell

Altered control of the rat cell cycle induced by adenovirus requires expression of transformation region E1A, but not of E1B, E2A, E2B, or late genes. We show here that neither E3 nor E4 is required, so the effect results directly from an E1A product. Mutants with defects in the 289-amino-acid (aa) E1A product had little or no effect on the rat cell cycle even at 1,000 IU per cell. A mutant (pm975) lacking the 243-aa E1A product altered cell cycle progression, but less efficiently than did wild-type virus. The 289-aa E1A protein is therefore essential for cell cycle effects; the 243-aa protein is also necessary for the full effect but cannot act alone. Mutants with altered 289-aa E1A proteins showed different extents of leak expression of viral early region E2A as the multiplicity was increased; each leaked more in human than in rat cells. dl312, with no E1A products, failed to produce E2A mRNA or protein at 1,000 IU per cell in rat cells but did so in some experiments in human cells. There appears to be a very strict dependence of viral early gene expression on E1A in rat cells, whereas dependence on E1A is more relaxed in HeLa cells, perhaps due to a cellular E1A-like function. Altered cell cycle control is more dependent on E1A function than is early viral gene expression.

Control functions of adenovirus transformation region E1A gene products in rat and human cells

1985 ◽  
Vol 5 (8) ◽  
pp. 1933-1939
Author(s):  
A J Bellett ◽  
P Li ◽  
E T David ◽  
E J Mackey ◽  
A W Braithwaite ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cell Cycle Control ◽  
Viral Gene Expression ◽  
Human Cells ◽  
Early Gene ◽  
Wild Type Virus ◽  
Viral Gene ◽  
Altered Cell

Altered control of the rat cell cycle induced by adenovirus requires expression of transformation region E1A, but not of E1B, E2A, E2B, or late genes. We show here that neither E3 nor E4 is required, so the effect results directly from an E1A product. Mutants with defects in the 289-amino-acid (aa) E1A product had little or no effect on the rat cell cycle even at 1,000 IU per cell. A mutant (pm975) lacking the 243-aa E1A product altered cell cycle progression, but less efficiently than did wild-type virus. The 289-aa E1A protein is therefore essential for cell cycle effects; the 243-aa protein is also necessary for the full effect but cannot act alone. Mutants with altered 289-aa E1A proteins showed different extents of leak expression of viral early region E2A as the multiplicity was increased; each leaked more in human than in rat cells. dl312, with no E1A products, failed to produce E2A mRNA or protein at 1,000 IU per cell in rat cells but did so in some experiments in human cells. There appears to be a very strict dependence of viral early gene expression on E1A in rat cells, whereas dependence on E1A is more relaxed in HeLa cells, perhaps due to a cellular E1A-like function. Altered cell cycle control is more dependent on E1A function than is early viral gene expression.

scholarly journals Regulation of Cell Division in Bacteria by Monitoring Genome Integrity and DNA Replication Status

2019 ◽  
Vol 202 (2) ◽  
Author(s):  
Peter E. Burby ◽  
Lyle A. Simmons
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Division ◽  
Dna Replication ◽  
Cell Cycle Progression ◽  
Genome Instability ◽  
Sos Response ◽  
Bacterial Cells ◽  
Cycle Progression ◽  
Content Type

ABSTRACT All organisms regulate cell cycle progression by coordinating cell division with DNA replication status. In eukaryotes, DNA damage or problems with replication fork progression induce the DNA damage response (DDR), causing cyclin-dependent kinases to remain active, preventing further cell cycle progression until replication and repair are complete. In bacteria, cell division is coordinated with chromosome segregation, preventing cell division ring formation over the nucleoid in a process termed nucleoid occlusion. In addition to nucleoid occlusion, bacteria induce the SOS response after replication forks encounter DNA damage or impediments that slow or block their progression. During SOS induction, Escherichia coli expresses a cytoplasmic protein, SulA, that inhibits cell division by directly binding FtsZ. After the SOS response is turned off, SulA is degraded by Lon protease, allowing for cell division to resume. Recently, it has become clear that SulA is restricted to bacteria closely related to E. coli and that most bacteria enforce the DNA damage checkpoint by expressing a small integral membrane protein. Resumption of cell division is then mediated by membrane-bound proteases that cleave the cell division inhibitor. Further, many bacterial cells have mechanisms to inhibit cell division that are regulated independently from the canonical LexA-mediated SOS response. In this review, we discuss several pathways used by bacteria to prevent cell division from occurring when genome instability is detected or before the chromosome has been fully replicated and segregated.

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