CLN- and CDC28-dependent Stimulation of CLN1 and CLN2 RNA Levels: Implications for Regulation by  -factor and by Cell Cycle Progression

1991 ◽  
Vol 56 (0) ◽  
pp. 1-8 ◽  
Author(s):  
F.R. Cross
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Stimulation Of ◽  
Rna Levels

scholarly journals The jun and fos protein families are both required for cell cycle progression in fibroblasts.

1991 ◽  
Vol 11 (9) ◽  
pp. 4466-4472 ◽  
Author(s):  
K Kovary ◽  
R Bravo
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Dna Synthesis ◽  
Cell Cycle Progression ◽  
S Phase ◽  
3T3 Cells ◽  
Cycle Progression ◽  
Serum Stimulation ◽  
Fos Protein ◽  
Stimulation Of

The expression of different members of the Jun and Fos families of transcription factors is rapidly induced following serum stimulation of quiescent fibroblasts. To determine whether these proteins are required for cell cycle progression, we microinjected affinity-purified antibodies directed against c-Fos, FosB, Fra-1, c-Jun, JunB, and JunD, and antibodies that recognize either the Fos or the Jun family of proteins, into Swiss 3T3 cells and determined their effects in cell cycle progression by monitoring DNA synthesis. We found that microinjection of anti-Fos and anti-Jun family antibodies efficiently blocked the entrance to the S phase of serum-stimulated or asynchronously growing cells. However, the antibodies against single members of the Fos family only partially inhibited DNA synthesis. In contrast, all three Jun antibodies prevented DNA synthesis more effectively than did any of the anti-Fos antibodies.

Cyclin-Dependent Kinase Phosphorylation of RUNX1/AML1 on Three Sites Increases Trans-Activation Potency and Stimulates Cell Proliferation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3351-3351
Author(s):  
Alan D. Friedman ◽  
Linsheng Zhang ◽  
Florence Bernardin Fried
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Aspartic Acid ◽  
Cell Cycle Progression ◽  
Hematopoietic Cell ◽  
Cyclin D3 ◽  
Cycle Progression ◽  
Inhibition Of Proliferation ◽  
Cdk Phosphorylation ◽  
Stimulation Of

RUNX1/AML1 regulates lineage-specific genes during hematopoiesis and also stimulates G1 cell cycle progression. CBFβ-SMMHC or AML1-ETO dominantly inhibit RUNX1 and slow G1 progression in hematopoietic cell lines or in murine or human marrow progenitors, cdk4, cyclin D2, or c-Myc overcome inhibition of proliferation by these CBF oncoproteins, exogenous RUNX1 stimulates G1 progression, and stimulation of G1 via deletion of p16INK4a or expression of E7 cooperates with CBFβ-SMMHC or TEL-AML1 to induce acute leukemia in mice. Induction of cdk4 or cyclin D3 transcription may underlie stimulation of G1 progression by RUNX1. Remarkably, the C. elegans ortholog of RUNX1, RNT-1, also stimulates G1 progression and couples stem cell proliferation with differentiation. Not only does RUNX1 regulate cell cycle progression, but in addition RUNX1 levels increase as hematopoietic cells progress from G1 to S and from S to G2/M. Within RUNX1, S48, S303, and S424 fit the cdk phosphorylation consensus, (S/T)PX(R/K). Phosphorylation of RUNX1 by cyclin dependent kinases on serine 303 was shown to mediate destabilization of RUNX1 in G2/M. We now find that S48 and S424 are also phosphorylated by cdk1 or cdk6. S48, S303, or S424 phosphopeptide antiserum that we developed specifically recognized kinased GST-RUNX1 and interacted with RUNX1 expressed in 293T cells or in the Ba/F3 hematopoietic cell line. S48 phosphorylation of RUNX1 paralleled total RUNX1 levels during cell cycle progression, S303 was more effectively phosphorylated in G2/M, and S424 in G1. Single, double, and triple mutation to alanine or to the partially phosphomimetic aspartic acid progressively diminished or increased trans-activation, such that the tripleA mutant activated a RUNX1 reporter 5-fold less potently than the tripleD mutant. Aspartic acid does not perfectly mimic serine phosphorylation, as illustrated by the much greater affinity of our antisera for wild-type RUNX1 versus RUNX1(tripleD), suggesting that the biologic effect of RUNX1 cdk phosphorylation is even more significant. The p300 co-activator retained interaction with the tripleA variant. The tripleD RUNX1 mutant rescued Ba/F3 cells from inhibition of proliferation by CBFβ-SMMHC more effectively than the tripleA mutant. Cdk phosphorylation of RUNX1 on three sites increases its ability to active transcription and to stimulate proliferation, potentially coupling entry of stem/progenitors into cycle with induction of genes required for hematopoietic lineage progression, such as those encoding myeloperoxidase, neutrophil elastase, the M-CSF receptor, and PU.1.

scholarly journals Distinct Signaling Pathways Mediate Stimulation of Cell Cycle Progression and Prevention of Apoptotic Cell Death by Estrogen in Rat Pituitary Tumor PR1 Cells

2003 ◽  
Vol 14 (12) ◽  
pp. 5051-5059 ◽  
Author(s):  
Simona Caporali ◽  
Manami Imai ◽  
Lucia Altucci ◽  
Massimo Cancemi ◽  
Silvana Caristi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Death ◽  
Dna Synthesis ◽  
Cell Survival ◽  
Pituitary Tumor ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Rat Pituitary ◽  
Stimulation Of

Estrogens control cell growth and viability in target cells via an interplay of genomic and extragenomic pathways not yet elucidated. Here, we show evidence that cell proliferation and survival are differentially regulated by estrogen in rat pituitary tumor PR1 cells. Pico- to femtomolar concentrations of 17β-estradiol (E2) are sufficient to foster PR1 cell proliferation, whereas nanomolar concentrations of the same are needed to prevent cell death that occurs at a high rate in these cells in the absence of hormone. Activation of endogenous (PRL) or transfected estrogen-responsive genes occurs at the same, higher concentrations of E2 required to promote cell survival, whereas stimulation of cyclin D3 expression and DNA synthesis occur at lower E2 concentrations. Similarly, the pure antiestrogen ICI 182,780 inhibits estrogen response element-dependent trans-activation and cell death more effectively than cyclin-cdk activity, G1-S transition, or DNA synthesis rate. In antiestrogen-treated and/or estrogen-deprived cells, death is due predominantly to apoptosis. Estrogen-induced cell survival, but not E2-dependent cell cycle progression, can be prevented by an inhibitor of c-Src kinase or by blockade of the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling pathway. These data indicate the coexistence of two distinguishable estrogen signaling pathways in PR1 cells, characterized by different functions and sensitivity to hormones and antihormones.

scholarly journals Silencing Lysine-Specific Histone Demethylase 1 (LSD1) Causes Increased HP1-Positive Chromatin, Stimulation of DNA Repair Processes, and Dysregulation of Proliferation by Chk1 Phosphorylation in Human Endothelial Cells

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1212 ◽  
Author(s):  
Wojtala ◽  
Dąbek ◽  
Rybaczek ◽  
Śliwińska ◽  
Świderska ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Endothelial Cells ◽  
Dna Repair ◽  
Cell Cycle Progression ◽  
Cell Model ◽  
Heterochromatin Protein 1 ◽  
Cycle Progression ◽  
Repair Processes ◽  
Lysine Residues ◽  
Stimulation Of

: The methylation of histone lysine residues modifies chromatin conformation and regulates the expression of genes implicated in cell metabolism. Lysine-specific demethylase 1 (LSD1) is a flavin-dependent monoamine oxidase that can demethylate mono- and dimethylated histone lysines 4 and 9 (H3K4 and H3K9). The removal of methyl groups from the lysine residues of histone and non-histone proteins was found to be an important regulatory factor of cell proliferation. However, its role has not been fully elucidated. In this study, we assessed LSD1-mediated cell cycle progression using a human endothelial cell model. The short hairpin RNA knockdown of LSD1 inhibits the G2/M phase of cell cycle progression by checkpoint kinase 1 (Chk1) phosphorylation (S137). We observed elevated DNA damage, which was consistent with the increased detection of double-strand breaks as well as purines and pyrimidines oxidation, which accompanied the activation of ATR/ATRIP signaling by H2AXS139 phosphorylation. The irreversible pharmacological inhibition of LSD1 by 2-phenylcyclopropylamine (2-PCPA) inactivated its enzymatic activity, causing significant changes in heterochromatin and euchromatin conformation assessed by chromatin assembly factor 1 subunit A (CAF1A) and heterochromatin protein 1 isoform α and γ (HP1α/γ) immunofluorescence analysis. We conclude that the knockdown of LSD1 in endothelial cells leads to increased HP1-positive chromatin, the stimulation of DNA repair processes, and the dysregulation of proliferation machinery.

scholarly journals Disruption of the Rb-Raf-1 Interaction Inhibits Tumor Growth and Angiogenesis

2004 ◽  
Vol 24 (21) ◽  
pp. 9527-9541 ◽  
Author(s):  
Piyali Dasgupta ◽  
Jiazhi Sun ◽  
Sheng Wang ◽  
Gina Fusaro ◽  
Vicki Betts ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Cell Cycle Progression ◽  
S Phase ◽  
Mitogen Activated Protein Kinase ◽  
Tubule Formation ◽  
Cycle Progression ◽  
Cyclin Dependent Kinases ◽  
Quiescent Cells ◽  
Stimulation Of

ABSTRACT The retinoblastoma tumor suppressor protein (Rb) plays a vital role in regulating mammalian cell cycle progression and inactivation of Rb is necessary for entry into S phase. Rb is inactivated by phosphorylation upon growth factor stimulation of quiescent cells, facilitating the transition from G1 phase to S phase. Although the signaling events after growth factor stimulation have been well characterized, it is not yet clear how these signals contact the cell cycle machinery. We had found previously that growth factor stimulation of quiescent cells lead to the direct binding of Raf-1 kinase to Rb, leading to its inactivation. Here we show that the Rb-Raf-1 interaction occurs prior to the activation of cyclin and/or cyclin-dependent kinases and facilitates normal cell cycle progression. Raf-1-mediated inactivation of Rb is independent of the mitogen-activated protein kinase cascade, as well as cyclin-dependent kinases. Binding of Raf-1 seemed to correlate with the dissociation of the chromatin remodeling protein Brg1 from Rb. Disruption of the Rb-Raf-1 interaction by a nine-amino-acid peptide inhibits Rb phosphorylation, cell proliferation, and vascular endothelial growth factor-mediated capillary tubule formation. Delivery of this peptide by a carrier molecule led to a 79% reduction in tumor volume and a 57% reduction in microvessel formation in nude mice. It appears that Raf-1 links mitogenic signaling to Rb and that disruption of this interaction could aid in controlling proliferative disorders.

scholarly journals Dual Stimulation of Ras/Mitogen-Activated Protein Kinase and Rhoa by Cell Adhesion to Fibronectin Supports Growth Factor–Stimulated Cell Cycle Progression

2000 ◽  
Vol 151 (7) ◽  
pp. 1413-1422 ◽  
Author(s):  
Erik H.J. Danen ◽  
Petra Sonneveld ◽  
Arnoud Sonnenberg ◽  
Kenneth M. Yamada
Keyword(s):  
Cell Cycle ◽  
Growth Factors ◽  
Growth Factor ◽  
Protein Kinase ◽  
Cell Cycle Progression ◽  
Mitogen Activated Protein Kinase ◽  
Cycle Progression ◽  
Extracellular Matrix Components ◽  
Mitogen Activated Protein ◽  
Stimulation Of

In cellular transformation, activated forms of the small GTPases Ras and RhoA can cooperate to drive cells through the G1 phase of the cell cycle. Here, we show that a similar but substrate-regulated mechanism is involved in the anchorage-dependent proliferation of untransformed NIH-3T3 cells. Among several extracellular matrix components tested, only fibronectin supported growth factor–induced, E2F-dependent S phase entry. Although all substrates supported the mitogen-activated protein kinase (MAPK) response to growth factors, RhoA activity was specifically enhanced on fibronectin. Moreover, induction of cyclin D1 and suppression of p21Cip/Waf occurred specifically, in a Rho-dependent fashion, in cells attached to fibronectin. This ability of fibronectin to stimulate both Ras/MAPK- and RhoA-dependent signaling can explain its potent cooperation with growth factors in the stimulation of cell cycle progression.

scholarly journals Expression and phosphorylation of fibroblast-growth-factor-inducible kinase (Fnk) during cell-cycle progression

1998 ◽  
Vol 333 (3) ◽  
pp. 655-660 ◽  
Author(s):  
Dan CHASE ◽  
Yang FENG ◽  
Brian HANSHEW ◽  
Jeffrey A. WINKLES ◽  
Dan L. LONGO ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Activity ◽  
Calf Serum ◽  
Fibroblast Growth ◽  
Cycle Progression ◽  
Quiescent Cells ◽  
Phosphatase Treatment ◽  
Sds Page ◽  
Stimulation Of

Fnk is a member of the polo family of cell-cycle-regulated serine/threonine kinases. We report here that it is present in serum-starved quiescent cells and that mitogenic stimulation of quiescent cells with calf serum results in the modification of a significant fraction of the Fnk pool. This modification results in a slower migrating form when analysed by SDS/PAGE. The modification is transient and by 9 h after stimulation all of the Fnk is again present as the faster migrating form. We also show that the Fnk protein increases in abundance as cells progress from G1 to mitosis and is post-translationally modified as cells enter and exit mitosis. The Fnk modification is again manifested as a slower migrating species by SDS/PAGE and is due to phosphorylation of the protein. The mitotic-specific phosphorylation of Fnk correlates with an increase in its kinase activity, and this activity is dramatically reduced by phosphatase treatment of mitotic Fnk immunoprecipitates. During the later stages of mitosis, Fnk is dephosphorylated such that, by the time the cells enter G1, it is all present as the dephosphorylated form. These results suggest that Fnk has two functions, one during the entry of cells into the cell cycle and a second during mitosis of cycling cells.

scholarly journals Requirement of protein kinase C zeta for stimulation of protein synthesis by insulin.

1997 ◽  
Vol 17 (9) ◽  
pp. 5184-5192 ◽  
Author(s):  
R Mendez ◽  
G Kollmorgen ◽  
M F White ◽  
R E Rhoads
Keyword(s):  
Cell Cycle ◽  
Protein Synthesis ◽  
Protein Kinase ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Kinase C ◽  
Pkc Zeta ◽  
General Protein Synthesis ◽  
General Protein ◽  
Stimulation Of

The ability of insulin to stimulate protein synthesis and cellular growth is mediated through the insulin receptor (IR), which phosphorylates Tyr residues in the insulin receptor substrate-signaling proteins (IRS-1 and IRS-2), Gab-1, and Shc. These phosphorylated substrates directly bind and activate enzymes such as phosphatidylinositol 3'-kinase (PI3K) and the guanine nucleotide exchange factor for p21Ras (GRB-2/SOS), which are in turn required for insulin-stimulated protein synthesis, cell cycle progression, and prevention of apoptosis. We have now shown that one or more members of the atypical protein kinase C group, as exemplified by the zeta isoform (PKC zeta), are downstream of IRS-1 and P13K and mediate the effect of insulin on general protein synthesis. Ectopic expression of constitutively activated PKC zeta eliminates the requirement of IRS-1 for general protein synthesis but not for insulin-stimulated activation of 70-kDa S6 kinase (p70S6K), synthesis of growth-regulated proteins (e.g., c-Myc), or mitogenesis. The fact that PKC zeta stimulates general protein synthesis but not activation of p70S6K indicates that PKC zeta activation does not involve the proto-oncogene Akt, which is also activated by PI3K. Yet insulin is still required for the stimulation of general protein synthesis in the presence of constitutively active PKC zeta and in the absence of IRS-1, suggesting a requirement for the convergence of the IRS-1/PI3K/PKC zeta pathway with one or more additional pathways emanating from the IR, e.g., Shc/SOS/p21Ras/mitogen-activated protein kinase. Thus, PI3K appears to represent a bifurcation in the insulin signaling pathway, one branch leading through PKC zeta to general protein synthesis and one, through Akt and the target of rapamycin (mTOR), to growth-regulated protein synthesis and cell cycle progression.

scholarly journals Role of p38 and ERK MAP kinase in proliferation of erythroid progenitors in response to stimulation by soluble and membrane isoforms of stem cell factor

Blood ◽  
2002 ◽  
Vol 100 (4) ◽  
pp. 1287-1293 ◽  
Author(s):  
Reuben Kapur ◽  
Saurabh Chandra ◽  
Ryan Cooper ◽  
Jennifer McCarthy ◽  
David A. Williams
Keyword(s):  
Cell Cycle ◽  
Map Kinase ◽  
Stem Cell Factor ◽  
Cell Cycle Progression ◽  
Erythroid Cell ◽  
Erythroid Cells ◽  
Inhibitory Effects ◽  
Cycle Progression ◽  
Map Kinase Pathways ◽  
Stimulation Of

Two alternatively spliced stem cell factor (SCF) transcripts encode protein products, which differ in the duration of membrane presentation. One form, soluble SCF (S-SCF) gets rapidly processed to yield predominantly secreted protein. The other form, membrane-associated SCF (MA-SCF) lacks the primary proteolytic cleavage site but is cleaved slowly from an alternate site, and thus represents a more stable membrane form of SCF. Mutants of SCF that lack the expression of MA-SCF (Steel-dickie) or possess a defect in its presentation (Steel17H) manifest deficiencies in erythroid cell development. In this study, we have compared the consequence(s) of activating Kit, the receptor for SCF by MA-SCF with S-SCF, and an obligate membrane-restricted (MR) form of SCF (MR-SCF) on erythroid cell survival, proliferation, cell cycle progression, and the activation of p38 and ERK MAP kinase pathways. Activation of Kit by MR-SCF was associated with a significantly lower incidence of apoptosis and cell death in erythroid cells compared to either other isoform. MR- or MA-SCF–induced stimulation of erythroid cells resulted in similar and significantly greater proliferation and cell cycle progression compared to soluble SCF. The increase in proliferation and cell cycle progression via MA- or MR-SCF stimulation correlated with sustained and enhanced activation of p38 and ERK MAP kinase pathways. In addition, MR- or MA-SCF–induced proliferation was more sensitive to the inhibitory effects of ERK inhibitor compared to S-SCF–induced proliferation. In contrast, soluble SCF-induced proliferation was more sensitive to the inhibitory effects of p38 inhibitor compared with MR- or MA-SCF. These results suggest that different isoforms of SCF may use different biochemical pathways in stimulation of survival and/or proliferation of erythroid cells.

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