scholarly journals Differential Modulation and Subsequent Blockade of Mitogenic Signaling and Cell Cycle Progression by Pasteurella multocida Toxin

2000 ◽  
Vol 68 (8) ◽  
pp. 4531-4538 ◽  
Author(s):  
Brenda A. Wilson ◽  
Lyaylya R. Aminova ◽  
Virgilio G. Ponferrada ◽  
Mengfei Ho
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Pasteurella Multocida ◽  
Morphological Changes ◽  
Cell Types ◽  
Vero Cells ◽  
3T3 Cells ◽  
Mitogenic Response ◽  
Cycle Progression ◽  
Swiss 3T3

ABSTRACT The intracellularly acting protein toxin of Pasteurella multocida (PMT) causes numerous effects in cells, including activation of inositol 1,4,5-trisphosphate (IP3) signaling, Ca2+ mobilization, protein phosphorylation, morphological changes, and DNA synthesis. The direct intracellular target of PMT responsible for activation of the IP3 pathway is the Gq/11α-protein, which stimulates phospholipase C (PLC) β1. The relationship between PMT-mediated activation of the Gq/11-PLC-IP3pathway and its ability to promote mitogenesis and cellular proliferation is not clear. PMT stimulation of p42/p44 mitogen-activated protein kinase occurs upstream via Gq/11-dependent transactivation of the epidermal growth factor receptor. We have further characterized the effects of PMT on the downstream mitogenic response and cell cycle progression in Swiss 3T3 and Vero cells. PMT treatment caused dramatic morphological changes in both cell lines. In Vero cells, limited multinucleation, nuclear fragmentation, and disruption of cytokinesis were also observed; however, a strong mitogenic response occurred only with Swiss 3T3 cells. Significantly, this mitogenic response was not sustained. Cell cycle analysis revealed that after the initial mitogenic response to PMT, both cell types subsequently arrested primarily in G1and became unresponsive to further PMT treatment. In Swiss 3T3 cells, PMT induced up-regulation of c-Myc; cyclins D1, D2, D3, and E; p21; PCNA; and the Rb proteins, p107 and p130. In Vero cells, PMT failed to up-regulate PCNA and cyclins D3 and E. We also found that the initial PMT-mediated up-regulation of several of these signaling proteins was not sustained, supporting the subsequent cell cycle arrest. The consequences of PMT entry thus depend on the differential regulation of signaling pathways within different cell types.

Activation of CCKb/gastrin receptor induces cell cycle progression in swiss 3T3 cells

2001 ◽  
Vol 120 (5) ◽  
pp. A508-A508
Author(s):  
E ZHUKOVA ◽  
J SINNETTSMITH ◽  
A BOLLES ◽  
H WONG ◽  
S YOUNG ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
3T3 Cells ◽  
Cycle Progression ◽  
Gastrin Receptor ◽  
Swiss 3T3

Activation of CCKb/gastrin receptor induces cell cycle progression in swiss 3T3 cells

2001 ◽  
Vol 120 (5) ◽  
pp. A508
Author(s):  
Elena Zhukova ◽  
James Sinnett-Smith ◽  
Angela Bolles ◽  
Helen Wong ◽  
Steve Young ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
3T3 Cells ◽  
Cycle Progression ◽  
Gastrin Receptor ◽  
Swiss 3T3

scholarly journals Calcium-dependent regulation of the cell cycle via a novel MAPK–NF-κB pathway in Swiss 3T3 cells

2004 ◽  
Vol 166 (5) ◽  
pp. 661-672 ◽  
Author(s):  
Violaine Sée ◽  
Nina K.M. Rajala ◽  
David G. Spiller ◽  
Michael R.H. White
Keyword(s):  
Cell Cycle ◽  
Intracellular Calcium ◽  
Real Time ◽  
Cell Cycle Progression ◽  
Mitogen Activated Protein Kinase ◽  
Calcium Signal ◽  
3T3 Cells ◽  
Cycle Progression ◽  
Calcium Dependent ◽  
Swiss 3T3

Nuclear factor kappa B (NF-κB) has been implicated in the regulation of cell proliferation and transformation. We investigated the role of the serum-induced intracellular calcium increase in the NF-κB–dependent cell cycle progression in Swiss 3T3 fibroblasts. Noninvasive photoactivation of a calcium chelator (Diazo-2) was used to specifically disrupt the transient rise in calcium induced by serum stimulation of starved Swiss 3T3 cells. The serum-induced intracellular calcium peak was essential for subsequent NF-κB activation (measured by real-time imaging of the dynamic p65 and IκBα fluorescent fusion proteins), cyclin D1 (CD1) promoter-directed transcription (measured by real-time luminescence imaging of CD1 promoter-directed firefly luciferase activity), and progression to cell division. We further showed that the serum-induced mitogen-activated protein kinase (MAPK) phosphorylation is calcium dependent. Inhibition of the MAPK- but not the PtdIns3K-dependent pathway inhibited NF-κB signaling, and further, CD1 transcription and cell cycle progression. These data suggest that a serum-dependent calcium signal regulates the cell cycle via a MAPK–NF-κB pathway in Swiss 3T3 cells.

scholarly journals Inhibition of cell proliferation by the Mad1 transcriptional repressor.

1996 ◽  
Vol 16 (6) ◽  
pp. 2796-2801 ◽  
Author(s):  
M F Roussel ◽  
R A Ashmun ◽  
C J Sherr ◽  
R N Eisenman ◽  
D E Ayer
Keyword(s):  
Cell Cycle ◽  
Dna Sequences ◽  
Cell Cycle Progression ◽  
Leucine Zipper ◽  
Ectopic Expression ◽  
Transcriptional Repressor ◽  
Cell Types ◽  
3T3 Cells ◽  
Cycle Progression ◽  
Tightly Coupled

Mad1 is a basic helix-loop-helix-leucine zipper protein that is induced upon differentiation of a number of distinct cell types. Mad1 dimerizes with Max and recognizes the same DNA sequences as do Myc:Max dimers. However, Mad1 and Myc appear to have opposing functions. Myc:Max heterodimers activate transcription while Mad:Max heterodimers repress transcription from the same promoter. In addition Mad1 has been shown to block the oncogenic activity of Myc. Here we show that ectopic expression of Mad1 inhibits the proliferative response of 3T3 cells to signaling through the colony-stimulating factor-1 (CSF-1) receptor. The ability of over-expressed Myc and cyclin D1 to complement the mutant CSF-1 receptor Y809F (containing a Y-to-F mutation at position 809) is also inhibited by Mad1. Cell cycle analysis of proliferating 3T3 cells transfected with Mad1 demonstrates a significant decrease in the fraction of cells in the S and G2/M phases and a concomitant increase in the fraction of G1 phase cells, indicating that Mad1 negatively influences cell cycle progression from the G1 to the S phase. Mutations in Mad1 which inhibit its activity as a transcription repressor also result in loss of Mad1 cell cycle inhibitory activity. Thus, the ability of Mad1 to inhibit cell cycle progression is tightly coupled to its function as a transcriptional repressor.

scholarly journals A NIMA-related Kinase, Fa2p, Localizes to a Novel Site in the Proximal Cilia of Chlamydomonas and Mouse Kidney Cells

2004 ◽  
Vol 15 (11) ◽  
pp. 5172-5186 ◽  
Author(s):  
Moe R. Mahjoub ◽  
M. Qasim Rasi ◽  
Lynne M. Quarmby
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cell Types ◽  
Mouse Kidney ◽  
Kidney Cells ◽  
Polycystic Kidney ◽  
Cycle Progression ◽  
Cystic Kidneys ◽  
Ciliary Function ◽  
The Relationship

Polycystic kidney disease and related syndromes involve dysregulation of cell proliferation in conjunction with ciliary defects. The relationship between cilia and cell cycle is enigmatic, but it may involve regulation by the NIMA-family of kinases (Neks). We previously showed that the Nek Fa2p is important for ciliary function and cell cycle in Chlamydomonas. We now show that Fa2p localizes to an important regulatory site at the proximal end of cilia in both Chlamydomonas and a mouse kidney cell line. Fa2p also is associated with the proximal end of centrioles. Its localization is dynamic during the cell cycle, following a similar pattern in both cell types. The cell cycle function of Fa2p is kinase independent, whereas its ciliary function is kinase dependent. Mice with mutations in Nek1 or Nek8 have cystic kidneys; therefore, our discovery that a member of this phylogenetic group of Nek proteins is localized to the same sites in Chlamydomonas and kidney epithelial cells suggests that Neks play conserved roles in the coordination of cilia and cell cycle progression.

scholarly journals Inactivation of CtIP Leads to Early Embryonic Lethality Mediated by G1 Restraint and to Tumorigenesis by Haploid Insufficiency

2005 ◽  
Vol 25 (9) ◽  
pp. 3535-3542 ◽  
Author(s):  
Phang-Lang Chen ◽  
Feng Liu ◽  
Suna Cai ◽  
Xiaoqin Lin ◽  
Aihua Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcriptional Repression ◽  
Cell Cycle Progression ◽  
Tumor Formation ◽  
3T3 Cells ◽  
Embryonic Fibroblasts ◽  
Cycle Progression ◽  
Early Embryonic Lethality ◽  
Nih 3T3 ◽  
Regulate Cell Cycle Progression

ABSTRACT CtIP interacts with a group of tumor suppressor proteins including RB (retinoblastoma protein), BRCA1, Ikaros, and CtBP, which regulate cell cycle progression through transcriptional repression as well as chromatin remodeling. However, how CtIP exerts its biological function in cell cycle progression remains elusive. To address this issue, we generated an inactivated Ctip allele in mice by inserting a neo gene into exon 5. The corresponding Ctip − / − embryos died at embryonic day 4.0 (E4.0), and the blastocysts failed to enter S phase but accumulated in G1, leading to a slightly elevated cell death. Mouse NIH 3T3 cells depleted of Ctip were arrested at G1 with the concomitant increase in hypophosphorylated Rb and Cdk inhibitors, p21. However, depletion of Ctip failed to arrest Rb − / − mouse embryonic fibroblasts (MEF) or human osteosarcoma Saos-2 cells at G1, suggesting that this arrest is RB dependent. Importantly, the life span of Ctip +/ − heterozygotes was shortened by the development of multiple types of tumors, predominantly, large lymphomas. The wild-type Ctip allele and protein remained detectable in these tumors, suggesting that haploid insufficiency of Ctip leads to tumorigenesis. Taken together, this finding uncovers a novel G1/S regulation in that CtIP counteracts Rb-mediated G1 restraint. Deregulation of this function leads to a defect in early embryogenesis and contributes, in part, to tumor formation.

scholarly journals Cellular Ras and Cyclin D1 Are Required during Different Cell Cycle Periods in Cycling NIH 3T3 Cells

1999 ◽  
Vol 19 (7) ◽  
pp. 4623-4632 ◽  
Author(s):  
Masahiro Hitomi ◽  
Dennis W. Stacey
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Cyclin D1 ◽  
Cell Cycle Progression ◽  
Time Lapse ◽  
S Phase ◽  
3T3 Cells ◽  
Cycle Progression ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

ABSTRACT Novel techniques were used to determine when in the cell cycle of proliferating NIH 3T3 cells cellular Ras and cyclin D1 are required. For comparison, in quiescent cells, all four of the inhibitors of cell cycle progression tested (anti-Ras, anti-cyclin D1, serum removal, and cycloheximide) became ineffective at essentially the same point in G1 phase, approximately 4 h prior to the beginning of DNA synthesis. To extend these studies to cycling cells, a time-lapse approach was used to determine the approximate cell cycle position of individual cells in an asynchronous culture at the time of inhibitor treatment and then to determine the effects of the inhibitor upon recipient cells. With this approach, anti-Ras antibody efficiently inhibited entry into S phase only when introduced into cells prior to the preceding mitosis, several hours before the beginning of S phase. Anti-cyclin D1, on the other hand, was an efficient inhibitor when introduced up until just before the initiation of DNA synthesis. Cycloheximide treatment, like anti-cyclin D1 microinjection, was inhibitory throughout G1 phase (which lasts a total of 4 to 5 h in these cells). Finally, serum removal blocked entry into S phase only during the first hour following mitosis. Kinetic analysis and a novel dual-labeling technique were used to confirm the differences in cell cycle requirements for Ras, cyclin D1, and cycloheximide. These studies demonstrate a fundamental difference in mitogenic signal transduction between quiescent and cycling NIH 3T3 cells and reveal a sequence of signaling events required for cell cycle progression in proliferating NIH 3T3 cells.

scholarly journals Cell Cycle Progression Regulates Biogenesis and Cellular Localization of Lipid Droplets

2019 ◽  
Vol 39 (9) ◽  
Author(s):  
André L. S. Cruz ◽  
Nina Carrossini ◽  
Leonardo K. Teixeira ◽  
Luis F. Ribeiro-Pinto ◽  
Patricia T. Bozza ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Lipid Accumulation ◽  
Lipid Droplets ◽  
Cell Cycle Progression ◽  
Cellular Transformation ◽  
3T3 Cells ◽  
Cycle Progression ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

ABSTRACTIntracellular lipid accumulation has been associated with a poor prognosis in cancer. We have previously reported the involvement of lipid droplets in cell proliferation in colon cancer cells, suggesting a role for these organelles in cancer development. In this study, we evaluate the role of lipid droplets in cell cycle regulation and cellular transformation. Cell cycle synchronization of NIH 3T3 cells revealed increased numbers and dispersed distribution of lipid droplets specifically during S phase. Also, the transformed cell lineage NIH 3T3-H-rasV12showed an accumulation of both lipid droplets and PLIN2 protein above the levels in NIH 3T3 cells.PLIN2gene overexpression, however, was not able to induce NIH 3T3 cell transformation, disproving the hypothesis thatPLIN2is an oncogene. Furthermore, positive PLIN2 staining was strongly associated with highly proliferative Ki-67-positive areas in human colon adenocarcinoma tissue samples. Taken together, these results indicate that cell cycle progression is associated with tight regulation of lipid droplets, a process that is altered in transformed cells, suggesting the existence of a mechanism that connects cell cycle progression and cell proliferation with lipid accumulation.

scholarly journals The Epstein-Barr Virus Immediate-Early Protein BZLF1 Induces Expression of E2F-1 and Other Proteins Involved in Cell Cycle Progression in Primary Keratinocytes and Gastric Carcinoma Cells

2002 ◽  
Vol 76 (24) ◽  
pp. 12543-12552 ◽  
Author(s):  
Amy Mauser ◽  
Elizabeth Holley-Guthrie ◽  
Adam Zanation ◽  
Wendall Yarborough ◽  
William Kaufmann ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cyclin E ◽  
Human Fibroblasts ◽  
Cell Types ◽  
S Phase ◽  
Cycle Progression ◽  
Stem Loop ◽  
Barr Virus ◽  
Early Protein

ABSTRACT The Epstein-Barr virus (EBV) immediate-early protein BZLF1 mediates the switch between the latent and lytic forms of EBV infection and has been previously shown to induce a G1/S block in cell cycle progression in some cell types. To examine the effect of BZLF1 on cellular gene expression, we performed microarray analysis on telomerase-immortalized human keratinocytes that were mock infected or infected with a control adenovirus vector (AdLacZ) or a vector expressing the EBV BZLF1 protein (AdBZLF1). Cellular genes activated by BZLF1 expression included E2F-1, cyclin E, Cdc25A, and a number of other genes involved in cell cycle progression. Immunoblot analysis confirmed that BZLF1 induced expression of E2F-1, cyclin E, Cdc25A, and stem loop binding protein (a protein known to be primarily expressed during S phase) in telomerase-immortalized keratinocytes. Similarly, BZLF1 increased expression of E2F-1, cyclin E, and stem loop binding protein (SLBP) in primary tonsil keratinocytes. In contrast, BZLF1 did not induce E2F-1 expression in normal human fibroblasts. Cell cycle analysis revealed that while BZLF1 dramatically blocked G1/S progression in normal human fibroblasts, it did not significantly affect cell cycle progression in primary human tonsil keratinocytes. Furthermore, in EBV-infected gastric carcinoma cells, the BZLF1-positive cells had an increased number of cells in S phase compared to the BZLF1-negative cells. Thus, in certain cell types (but not others), BZLF1 enhances expression of cellular proteins associated with cell cycle progression, which suggests that an S-phase-like environment may be advantageous for efficient lytic EBV replication in some cell types.

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