scholarly journals Phosphatidylinositol-4-phosphate 5-Kinase 1α Modulates Ribosomal RNA Gene Silencing through Its Interaction with Histone H3 Lysine 9 Trimethylation and Heterochromatin Protein HP1-α

2015 ◽  
Vol 290 (34) ◽  
pp. 20893-20903 ◽  
Author(s):  
Rajarshi Chakrabarti ◽  
Sulagna Sanyal ◽  
Amit Ghosh ◽  
Kaushik Bhar ◽  
Chandrima Das ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Gene Transcription ◽  
Cell Cycle Progression ◽  
Gene Activation ◽  
Cellular Motility ◽  
Heterochromatin Protein ◽  
Cyclical Pattern ◽  
Rdna Loci ◽  
Cytoskeletal Dynamics ◽  
Phosphatidylinositol 4

Phosphoinositide signaling has been implicated in the regulation of numerous cellular processes including cytoskeletal dynamics, cellular motility, vesicle trafficking, and gene transcription. Studies have also shown that nuclear phosphoinositide(s) regulates processes such as mRNA export, cell cycle progression, gene transcription, and DNA repair. We have shown previously that the nuclear form of phosphatidylinositol-4-phosphate 5-kinase 1α (PIP5K), the enzyme responsible for phosphatidylinositol 4,5-bisphosphate synthesis, is modified by small ubiquitin-like modifier (SUMO)-1. In this study, we have shown that due to the site-specific Lys to Ala mutations of PIP5K at Lys-244 and Lys-490, it is unable to localize in the nucleus and nucleolus, respectively. Furthermore, by using chromatin immunoprecipitation assays, we have observed that PIP5K associates with the chromatin silencing complex constituted of H3K9me3 and heterochromatin protein 1α at multiple ribosomal DNA (rDNA) loci. These interactions followed a definite cyclical pattern of occupancy (mostly G1) and release from the rDNA loci (G1/S) throughout the cell cycle. Moreover, the immunoprecipitation results clearly demonstrate that PIP5K SUMOylated at Lys-490 interacts with components of the chromatin silencing machinery, H3K9me3 and heterochromatin protein 1α. However, PIP5K does not interact with the gene activation signature protein H3K4me3. This study, for the first time, demonstrates that PIP5K, an enzyme actively associated with lipid modification pathway, has additional roles in rDNA silencing.

scholarly journals A Genetic Screen for Suppressors and Enhancers of the Drosophila Cdk1-Cyclin B Identifies Maternal Factors That Regulate Microtubule and Microfilament Stability

Genetics ◽  
2002 ◽  
Vol 162 (3) ◽  
pp. 1179-1195 ◽  
Author(s):  
Jun-Yuan Ji ◽  
Marjan Haghnia ◽  
Cory Trusty ◽  
Lawrence S B Goldstein ◽  
Gerold Schubiger
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Genetic Screen ◽  
Cyclin B ◽  
Gene Products ◽  
Nuclear Movement ◽  
Cell Cycles ◽  
Major Mechanism ◽  
Cytoskeletal Dynamics ◽  
Chromosome Bridges

Abstract Coordination between cell-cycle progression and cytoskeletal dynamics is important for faithful transmission of genetic information. In early Drosophila embryos, increasing maternal cyclin B leads to higher Cdk1-CycB activity, shorter microtubules, and slower nuclear movement during cycles 5-7 and delays in nuclear migration to the cortex at cycle 10. Later during cycle 14 interphase of six cycB embryos, we observed patches of mitotic nuclei, chromosome bridges, abnormal nuclear distribution, and small and large nuclei. These phenotypes indicate disrupted coordination between the cell-cycle machinery and cytoskeletal function. Using these sensitized phenotypes, we performed a dosage-sensitive genetic screen to identify maternal proteins involved in this process. We identified 10 suppressors classified into three groups: (1) gene products regulating Cdk1 activities, cdk1 and cyclin A; (2) gene products interacting with both microtubules and microfilaments, Actin-related protein 87C; and (3) gene products interacting with microfilaments, chickadee, diaphanous, Cdc42, quail, spaghetti-squash, zipper, and scrambled. Interestingly, most of the suppressors that rescue the astral microtubule phenotype also reduce Cdk1-CycB activities and are microfilament-related genes. This suggests that the major mechanism of suppression relies on the interactions among Cdk1-CycB, microtubule, and microfilament networks. Our results indicate that the balance among these different components is vital for normal early cell cycles and for embryonic development. Our observations also indicate that microtubules and cortical microfilaments antagonize each other during the preblastoderm stage.

scholarly journals Regulation of Phosphoinositide Levels by the Phospholipid Transfer Protein Sec14p Controls Cdc42p/p21-Activated Kinase-Mediated Cell Cycle Progression at Cytokinesis

2007 ◽  
Vol 6 (10) ◽  
pp. 1814-1823 ◽  
Author(s):  
Alicia G. Howe ◽  
Gregory D. Fairn ◽  
Kendra MacDonald ◽  
Vytas A. Bankaitis ◽  
Christopher R. McMaster
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Cell Cycle Progression ◽  
Rho Gtpase ◽  
Genomic Library ◽  
Vesicular Transport ◽  
Temperature Sensitive ◽  
Transfer Protein ◽  
Phosphatidylinositol Transfer ◽  
Phosphatidylinositol 4

ABSTRACT Sec14p is an essential phosphatidylcholine/phosphatidylinositol transfer protein with a well-described role in the regulation of Golgi apparatus-derived vesicular transport in yeast. Inactivation of the CDP-choline pathway for phosphatidylcholine synthesis allows cells to survive in the absence of Sec14p function through restoration of Golgi vesicular transport capability. In this study, Saccharomyces cerevisiae cells containing a SEC14 temperature-sensitive allele along with an inactivated CDP-choline pathway were transformed with a high-copy-number yeast genomic library. Genes whose increased expression inhibited cell growth in the absence of Sec14p function were identified. Increasing levels of the Rho GTPase Cdc42p and its direct effector kinases Cla4p and Ste20p prevented the growth of cells lacking Sec14p and CDP-choline pathway function. Growth suppression was accompanied by an increase in large and multiply budded cells. This effect on polarized cell growth did not appear to be due to an inability to establish cell polarity, since both the actin cytoskeleton and localization of the septin Cdc12p were unaffected by increased expression of Cdc42p, Cla4p, or Ste20p. Nuclei were present in both the mother cell and the emerging bud, consistent with Sec14p regulation of the cell cycle subsequent to anaphase but prior to cytokinesis/septum breakdown. Increased expression of phosphatidylinositol 4-kinases and phosphatidylinositol 4-phosphate 5-kinase prevented growth arrest by CDC42, CLA4, or STE20 upon inactivation of Sec14p function. Sec14p regulation of phosphoinositide levels affects cytokinesis at the level of the Cdc42p/Cla4p/Ste20p signaling cascade.

scholarly journals Human E2F-1 Reactivates Cell Cycle Progression in Ventricular Myocytes and Represses Cardiac Gene Transcription

1996 ◽  
Vol 179 (2) ◽  
pp. 402-411 ◽  
Author(s):  
Lorrie A Kirshenbaum ◽  
Maha Abdellatif ◽  
Subendu Chakraborty ◽  
Michael D Schneider
Keyword(s):  
Cell Cycle ◽  
Gene Transcription ◽  
Cell Cycle Progression ◽  
Ventricular Myocytes ◽  
Cycle Progression ◽  
Cardiac Gene

scholarly journals CDK12: A Potent Target and Biomarker for Human Cancer Therapy

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1483 ◽  
Author(s):  
Shujing Liang ◽  
Lifang Hu ◽  
Zixiang Wu ◽  
Zhihao Chen ◽  
Shuyu Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cancer Therapy ◽  
Gene Transcription ◽  
Rna Splicing ◽  
Cell Cycle Progression ◽  
Current Knowledge ◽  
Human Cancer ◽  
Cellular Processes ◽  
Potential Target ◽  
Human Cancers

Cyclin-dependent kinases (CDKs) are a group of serine/threonine protein kinases and play crucial roles in various cellular processes by regulating cell cycle and gene transcription. Cyclin-dependent kinase 12 (CDK12) is an important transcription-associated CDK. It shows versatile roles in regulating gene transcription, RNA splicing, translation, DNA damage response (DDR), cell cycle progression and cell proliferation. Recently, increasing evidence demonstrates the important role of CDK12 in various human cancers, illustrating it as both a biomarker of cancer and a potential target for cancer therapy. Here, we summarize the current knowledge of CDK12, and review the research advances of CDK12′s biological functions, especially its role in human cancers and as a potential target and biomarker for cancer therapy.

Microtubule-associated protein/microtubule affinity-regulating kinase 4 (MARK4) plays a role in cell cycle progression and cytoskeletal dynamics

2014 ◽  
Vol 93 (8-9) ◽  
pp. 355-365 ◽  
Author(s):  
Davide Rovina ◽  
Laura Fontana ◽  
Laura Monti ◽  
Chiara Novielli ◽  
Nicolò Panini ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Cytoskeletal Dynamics

scholarly journals Retinoblastoma Protein Regulation by the COP9 Signalosome

2007 ◽  
Vol 18 (4) ◽  
pp. 1179-1186 ◽  
Author(s):  
Zakir Ullah ◽  
Martin S. Buckley ◽  
David N. Arnosti ◽  
R. William Henry
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Target Gene ◽  
Control Cell ◽  
Gene Activation ◽  
Active Role ◽  
Cop9 Signalosome ◽  
Gene Promoters ◽  
Developmentally Regulated ◽  
Regulated Gene Expression

Similar to their human counterparts, the Drosophila Rbf1 and Rbf2 Retinoblastoma family members control cell cycle and developmentally regulated gene expression. Increasing evidence suggests that Rbf proteins rely on multiprotein complexes to control target gene transcription. We show here that the developmentally regulated COP9 signalosome (CSN) physically interacts with Rbf2 during embryogenesis. Furthermore, the CSN4 subunit of the COP9 signalosome co-occupies Rbf target gene promoters with Rbf1 and Rbf2, suggesting an active role for the COP9 signalosome in transcriptional regulation. The targeted knockdown of individual CSN subunits leads to diminished Rbf1 and Rbf2 levels and to altered cell cycle progression. The proteasome-mediated destruction of Rbf1 and Rbf2 is increased in cells and embryos with diminished COP9 activity, suggesting that the COP9 signalosome protects Rbf proteins during embryogenesis. Previous evidence has linked gene activation to protein turnover via the promoter-associated proteasome. Our findings suggest that Rbf repression may similarly involve the proteasome and the promoter-associated COP9 signalosome, serving to extend Rbf protein lifespan and enable appropriate programs of retinoblastoma gene control during development.

scholarly journals HDAC8-dependent deacetylation of PKM2 directs nuclear localization and glycolysis to promote proliferation in hepatocellular carcinoma

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Ruixue Zhang ◽  
Mengqin Shen ◽  
Chunhua Wu ◽  
Yumei Chen ◽  
Jiani Lu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Gene Transcription ◽  
Nuclear Localization ◽  
Cell Cycle Progression ◽  
Post Translational Modification ◽  
Cycle Progression ◽  
Ccnd1 Gene ◽  
Metabolic Protein ◽  
Rate Limiting

AbstractPyruvate kinase M2 (PKM2) is not only a key rate-limiting enzyme that guides glycolysis, but also acts as a non-metabolic protein in regulating gene transcription. In recent years, a series of studies have confirmed that post-translational modification has become an important mechanism for regulating the function of PKM2, which in turn affects tumorigenesis. In this study, we found that K62 residues were deacetylated, which is related to the prognosis of HCC. Further studies indicate that HDAC8 binds and deacetylates the K62 residue of PKM2. Mechanistically, K62 deacetylation facilitate PKM2 transport into the nucleus and bind β-catenin, thereby promoting CCND1 gene transcription and cell cycle progression. In addition, the deacetylation of K62 affects the enzyme activity of PKM2 and the flux of glucose metabolism. Therefore, these results suggest that HDAC8 / PKM2 signaling may become a new target for the treatment of HCC.

scholarly journals Nuclear Myosin 1c Facilitates the Chromatin Modifications Required to Activate rRNA Gene Transcription and Cell Cycle Progression

PLoS Genetics ◽  
2013 ◽  
Vol 9 (3) ◽  
pp. e1003397 ◽  
Author(s):  
Aishe Sarshad ◽  
Fatemeh Sadeghifar ◽  
Emilie Louvet ◽  
Raffaele Mori ◽  
Stefanie Böhm ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Gene Transcription ◽  
Cell Cycle Progression ◽  
Rrna Gene ◽  
Chromatin Modifications ◽  
Cycle Progression

Constitutive and Interleukin-7/Interleukin-15 Stimulated DNA Binding of Myc, Jun, and Novel Myc-Like Proteins in Cutaneous T-Cell Lymphoma Cells

Blood ◽  
1999 ◽  
Vol 93 (1) ◽  
pp. 260-267 ◽  
Author(s):  
J-Z. Qin ◽  
R. Dummer ◽  
G. Burg ◽  
U. Döbbeling
Keyword(s):  
Cell Cycle ◽  
Dna Binding ◽  
Cell Lines ◽  
Gene Transcription ◽  
Cell Cycle Progression ◽  
Cell Lymphoma ◽  
Gene Families ◽  
Cutaneous T Cell Lymphoma ◽  
Cycle Progression ◽  
Interleukin 7

Abstract Members of the Myc and Jun/Fos gene families have been found to be expressed in late stages of cutaneous T-cell lymphoma (CTCL) and may be responsible for the transition from low-grade to high-grade tumors. The composition of these complexes is an important parameter, as the different homo- and heterodimeric jun and myc complexes can have gene transcription activating or suppressing activities. We determined the composition of the jun and myc DNA-binding complexes in three CTCL cell lines and malignant cells of seven Sézary patients by electrophoretic mobility shift assays (EMSAs) and “supershift” assays in which specific antibodies against the different members of the tested gene families were included in the binding reactions. Complexes containing JunD were found in three cell lines and two patients. The three cell lines and one patient contained also c-Myc/Max heterodimers. Because c-Myc/Max heterodimers are strong gene transcription activators and are necessary for cell-cycle progression, they may play a role in the progression of CTCL. JunD may also promote cell-cycle progression and influence the expression of cell death survival genes. Interleukin-7 (IL-7) and IL-15, which have been identified as growth factors for CTCL cells, stimulated the DNA binding of JunD and two novel c-Myc recognition site (E-box) binding proteins, but not the DNA binding of c-Myc/Max heterodimers.

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