scholarly journals TORC2 dependent phosphorylation modulates calcium regulation of fission yeast myosin

2018 ◽  
Author(s):  
Karen Baker ◽  
Irene A. Gyamfi ◽  
Gregory I. Mashanov ◽  
Justin E. Molloy ◽  
Michael A. Geeves ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Fission Yeast ◽  
Single Molecule ◽  
Cell Cycle Progression ◽  
Neck Region ◽  
Dependent Manner ◽  
Meiotic Cell ◽  
Cycle Progression ◽  
Cellular Environment

AbstractAll cells have the ability to respond to changes in their environment. Signalling networks modulate cytoskeleton and membrane organisation to impact cell cycle progression, polarised cell growth and multicellular development according to the environmental setting. Using diverse in vitro, in vivo and single molecule techniques we have explored the role of myosin-1 signalling in regulating endocytosis during both mitotic and meiotic cell cycles. We have established that a conserved serine within the neck region of the sole fission yeast myosin-1 is phosphorylated in a TORC2 dependent manner to modulate myosin function. Myo1 neck phosphorylation brings about a change in the conformation of the neck region and modifies its interaction with calmodulins, Myo1 dynamics at endocytic foci, and promotes calcium dependent switching between different calmodulin light chains. These data provide insight into a novel mechanism by which myosin neck phosphorylation modulates acto-myosin dynamics to control polarised cell growth in response to mitotic and meiotic cell-cycle progression and the cellular environment.

scholarly journals Compartmentalized nodes control mitotic entry signaling in fission yeast

2013 ◽  
Vol 24 (12) ◽  
pp. 1872-1881 ◽  
Author(s):  
Lin Deng ◽  
James B. Moseley
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Fission Yeast ◽  
Cell Polarity ◽  
Cell Cycle Progression ◽  
Interaction Network ◽  
Yeast Cells ◽  
Cell Cortex ◽  
Cycle Progression ◽  
Mitotic Entry

Cell cycle progression is coupled to cell growth, but the mechanisms that generate growth-dependent cell cycle progression remain unclear. Fission yeast cells enter into mitosis at a defined size due to the conserved cell cycle kinases Cdr1 and Cdr2, which localize to a set of cortical nodes in the cell middle. Cdr2 is regulated by the cell polarity kinase Pom1, suggesting that interactions between cell polarity proteins and the Cdr1-Cdr2 module might underlie the coordination of cell growth and division. To identify the molecular connections between Cdr1/2 and cell polarity, we performed a comprehensive pairwise yeast two-hybrid screen. From the resulting interaction network, we found that the protein Skb1 interacted with both Cdr1 and the Cdr1 inhibitory target Wee1. Skb1 inhibited mitotic entry through negative regulation of Cdr1 and localized to both the cytoplasm and a novel set of cortical nodes. Skb1 nodes were distinct structures from Cdr1/2 nodes, and artificial targeting of Skb1 to Cdr1/2 nodes delayed entry into mitosis. We propose that the formation of distinct node structures in the cell cortex controls signaling pathways to link cell growth and division.

scholarly journals Tryprostatin A, a specific and novel inhibitor of microtubule assembly

1998 ◽  
Vol 333 (3) ◽  
pp. 543-548 ◽  
Author(s):  
Takeo USUI ◽  
Masuo KONDOH ◽  
Cheng-Bin CUI ◽  
Tadanori MAYUMI ◽  
Hiroyuki OSADA
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Cell Cycle Progression ◽  
Microtubule Assembly ◽  
Inhibition Mechanism ◽  
Dependent Manner ◽  
Cycle Progression ◽  
Terminal Domain ◽  
M Phase

We have investigated the cell cycle inhibition mechanism and primary target of tryprostatin A (TPS-A) purified from Aspergillus fumigatus. TPS-A inhibited cell cycle progression of asynchronously cultured 3Y1 cells in the M phase in a dose- and time-dependent manner. In contrast, TPS-B (the demethoxy analogue of TPS-A) showed cell-cycle non-specific inhibition on cell growth even though it inhibited cell growth at lower concentrations than TPS-A. TPS-A treatment induced the reversible disruption of the cytoplasmic microtubules of 3Y1 cells as observed by indirect immunofluorescence microscopy in the range of concentrations that specifically inhibited M-phase progression. TPS-A inhibited the assembly in vitro of microtubules purified from bovine brains (40% inhibition at 250 µM); however, there was little or no effect on the self-assembly of purified tubulin when polymerization was induced by glutamate even at 250 µM TPS-A. TPS-A did not inhibit assembly promoted by taxol or by digestion of the C-terminal domain of tubulin. However, TPS-A blocked the tubulin assembly induced by inducers interacting with the C-terminal domain, microtubule-associated protein 2 (MAP2), tau and poly-(l-lysine). These results indicate that TPS-A is a novel inhibitor of MAP-dependent microtubule assembly and, through the disruption of the microtubule spindle, specifically inhibits cell cycle progression at the M phase.

scholarly journals Oncogenic role of ALX3 in cervical cancer cells through KDM2B-mediated histone demethylation of CDC25A

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jinhong Qi ◽  
Li Zhou ◽  
Dongqing Li ◽  
Jingyuan Yang ◽  
He Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cell Cycle Progression ◽  
Cervical Squamous Cell Carcinoma ◽  
Cycle Progression ◽  
Normal Tissues ◽  
Positive Regulator ◽  
Cervical Cancer Cells

Abstract Background Cell division cycle 25A (CDC25A) is a well-recognized regulator of cell cycle progression and is involved in cancer development. This work focused on the function of CDC25A in cervical cancer cell growth and the molecules involved. Methods A GEO dataset GSE63514 comprising data of cervical squamous cell carcinoma (CSCC) tissues was used to screen the aberrantly expressed genes in cervical cancer. The CDC25A expression in cancer and normal tissues was predicted in the GEPIA database and that in CSCC and normal cells was determined by RT-qPCR and western blot assays. Downregulation of CDC25A was introduced in CSCC cells to explore its function in cell growth and the cell cycle progression. The potential regulators of CDC25A activity and the possible involved signaling were explored. Results CDC25A was predicted to be overexpressed in CSCC, and high expression of CDC25A was observed in CSCC cells. Downregulation of CDC25A in ME180 and C33A cells reduced cell proliferation and blocked cell cycle progression, and it increased cell apoptosis. ALX3 was a positive regulator of CDC25A through transcription promotion. It recruited a histone demethylase, lysine demethylase 2B (KDM2B), to the CDC25A promoter, which enhanced CDC25A expression through demethylation of H3k4me3. Overexpression of ALX3 in cells blocked the inhibitory effects of CDC25A silencing. CDC25A was found as a positive regulator of the PI3K/Akt signaling pathway. Conclusion This study suggested that the ALX3 increased CDC25A expression through KDM2B-mediated demethylation of H3K4me3, which induced proliferation and cell cycle progression of cervical cancer cells.

Involvement of caveolin-1 in meiotic cell-cycle progression in Caenorhabditis elegans

10.1038/10100 ◽  
1999 ◽  
Vol 1 (2) ◽  
pp. 127-129 ◽  
Author(s):  
Jochen Scheel ◽  
Jagan Srinivasan ◽  
Ulrike Honnert ◽  
Annemarie Henske ◽  
Teymuras V. Kurzchalia
Keyword(s):  
Cell Cycle ◽  
Caenorhabditis Elegans ◽  
Cell Cycle Progression ◽  
Meiotic Cell ◽  
Cycle Progression ◽  
Caveolin 1

scholarly journals CNOT 6L couples the selective degradation of maternal transcripts to meiotic cell cycle progression in mouse oocyte

2018 ◽  
Vol 37 (24) ◽  
Author(s):  
Qian‐Qian Sha ◽  
Jia‐Li Yu ◽  
Jing‐Xin Guo ◽  
Xing‐Xing Dai ◽  
Jun‐Chao Jiang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Mouse Oocyte ◽  
Meiotic Cell ◽  
Cycle Progression ◽  
Selective Degradation ◽  
Maternal Transcripts

scholarly journals TORC2-Gad8-dependent myosin phosphorylation modulates regulation by calcium

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Karen Baker ◽  
Irene A Gyamfi ◽  
Gregory I Mashanov ◽  
Justin E Molloy ◽  
Michael A Geeves ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Cell Cycle Progression ◽  
Actin Polymerization ◽  
Neck Region ◽  
Signaling Networks ◽  
Tor Signaling ◽  
Multicellular Development ◽  
Membrane Reorganization ◽  
And Function

Cells respond to changes in their environment through signaling networks that modulate cytoskeleton and membrane organization to coordinate cell-cycle progression, polarized cell growth and multicellular development. Here, we define a novel regulatory mechanism by which the motor activity and function of the fission yeast type one myosin, Myo1, is modulated by TORC2-signalling-dependent phosphorylation. Phosphorylation of the conserved serine at position 742 (S742) within the neck region changes both the conformation of the neck region and the interactions between Myo1 and its associating calmodulin light chains. S742 phosphorylation thereby couples the calcium and TOR signaling networks that are involved in the modulation of myosin-1 dynamics to co-ordinate actin polymerization and membrane reorganization at sites of endocytosis and polarised cell growth in response to environmental and cell-cycle cues.

scholarly journals Carvedilol Inhibits Angiotensin II-Induced Proliferation and Contraction in Hepatic Stellate Cells through the RhoA/Rho-Kinase Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Ying Wu ◽  
Zhen Li ◽  
Sining Wang ◽  
Aiyuan Xiu ◽  
Chunqing Zhang
Keyword(s):  
Cell Cycle ◽  
Angiotensin Ii ◽  
Liver Fibrosis ◽  
Cell Cycle Progression ◽  
Rho Kinase ◽  
Cell Counting ◽  
Type I ◽  
Dependent Manner ◽  
Ang Ii ◽  
Cycle Progression

Aim. Carvedilol is a nonselective beta-blocker used to reduce portal hypertension. This study investigated the effects and potential mechanisms of carvedilol in angiotensin II- (Ang II-) induced hepatic stellate cell (HSC) proliferation and contraction. Methods. The effect of carvedilol on HSC proliferation was measured by Cell Counting Kit-8 (CCK-8). Cell cycle progression and apoptosis in HSCs were determined by flow cytometry. A collagen gel assay was used to confirm HSC contraction. The extent of liver fibrosis in mice was evaluated by hematoxylin-eosin (H&E) and Sirius Red staining. Western blot analyses were performed to detect the expression of collagen I, collagen III, α-smooth muscle actin (α-SMA), Ang II type I receptor (AT1R), RhoA, Rho-kinase 2 (ROCK2), and others. Results. The results showed that carvedilol inhibited HSC proliferation and arrested the cell cycle at the G0/G1 phase in a dose-dependent manner. Carvedilol also modulated Bcl-2 family proteins and increased apoptosis in Ang II-treated HSCs. Furthermore, carvedilol inhibited HSC contraction induced by Ang II, an effect that was associated with AT1R-mediated RhoA/ROCK2 pathway interference. In addition, carvedilol reduced α-SMA expression and collagen deposition and attenuated liver fibrosis in carbon tetrachloride (CCl4)-treated mice. The in vivo data further confirmed that carvedilol inhibited the expression of angiotensin-converting enzyme (ACE), AT1R, RhoA, and ROCK2. Conclusions. The results indicated that carvedilol dose-dependently inhibited Ang II-induced HSC proliferation by impeding cell cycle progression, thus alleviating hepatic fibrosis. Furthermore, carvedilol could inhibit Ang II-induced HSC contraction by interfering with the AT1R-mediated RhoA/ROCK2 pathway.

scholarly journals An Alternatively Translated Connexin 43 Isoform, GJA1-11k, Localizes to the Nucleus and Can Inhibit Cell Cycle Progression

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 473
Author(s):  
Irina Epifantseva ◽  
Shaohua Xiao ◽  
Rachel E. Baum ◽  
André G. Kléber ◽  
TingTing Hong ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Gap Junction ◽  
Connexin 43 ◽  
Cell Cycle Progression ◽  
Tumor Formation ◽  
Full Length ◽  
Cycle Progression ◽  
Junction Protein ◽  
Truncated Isoforms

Connexin 43 (Cx43) is a gap junction protein that assembles at the cell border to form intercellular gap junction (GJ) channels which allow for cell–cell communication by facilitating the rapid transmission of ions and other small molecules between adjacent cells. Non-canonical roles of Cx43, and specifically its C-terminal domain, have been identified in the regulation of Cx43 trafficking, mitochondrial preconditioning, cell proliferation, and tumor formation, yet the mechanisms are still being explored. It was recently identified that up to six truncated isoforms of Cx43 are endogenously produced via alternative translation from internal start codons in addition to full length Cx43, all from the same mRNA produced by the gene GJA1. GJA1-11k, the 11kDa alternatively translated isoform of Cx43, does not have a known role in the formation of gap junction channels, and little is known about its function. Here, we report that over expressed GJA1-11k, unlike the other five truncated isoforms, preferentially localizes to the nucleus in HEK293FT cells and suppresses cell growth by limiting cell cycle progression from the G0/G1 phase to the S phase. Furthermore, these functions are independent of the channel-forming full-length Cx43 isoform. Understanding the apparently unique role of GJA1-11k and its generation in cell cycle regulation may uncover a new target for affecting cell growth in multiple disease models.

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