Helicobacter pylori Releases a Factor(s) Inhibiting Cell Cycle Progression of Human Gastric Cell Lines by Affecting Cyclin E/cdk2 Kinase Activity and Rb Protein Phosphorylation through Enhanced p27KIP1 Protein Expression

2002 ◽  
Vol 281 (1) ◽  
pp. 128-139 ◽  
Author(s):  
P Sommi
Keyword(s):  
Cell Cycle ◽  
Helicobacter Pylori ◽  
Protein Expression ◽  
Protein Phosphorylation ◽  
Cell Cycle Progression ◽  
Kinase Activity ◽  
Cycle Progression ◽  
Rb Protein ◽  
P27kip1 Protein ◽  
Gastric Cell

Helicobacter pylori inhibits gastric cell cycle progression

2000 ◽  
Vol 2 (10) ◽  
pp. 1159-1169 ◽  
Author(s):  
Amel Ahmed ◽  
Duane Smoot ◽  
George Littleton ◽  
Robert Tackey ◽  
Curla S. Walters ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Helicobacter Pylori ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Gastric Cell

scholarly journals Ras controls growth, survival and differentiation in the Drosophila eye by different thresholds of MAP kinase activity

Development ◽  
2001 ◽  
Vol 128 (9) ◽  
pp. 1687-1696 ◽  
Author(s):  
K. Halfar ◽  
C. Rommel ◽  
H. Stocker ◽  
E. Hafen
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Activity ◽  
Photoreceptor Cells ◽  
Loss Of Function ◽  
Cellular Functions ◽  
Partial Loss ◽  
Cycle Progression ◽  
Mapk Activity ◽  
Dividing Cells

Ras mediates a plethora of cellular functions during development. In the developing eye of Drosophila, Ras performs three temporally separate functions. In dividing cells, it is required for growth but is not essential for cell cycle progression. In postmitotic cells, it promotes survival and subsequent differentiation of ommatidial cells. In the present paper, we have analyzed the different roles of Ras during eye development by using molecularly defined complete and partial loss-of-function mutations of Ras. We show that the three different functions of Ras are mediated by distinct thresholds of MAPK activity. Low MAPK activity prolongs cell survival and permits differentiation of R8 photoreceptor cells while high or persistent MAPK activity is sufficient to precociously induce R1-R7 photoreceptor differentiation in dividing cells.

scholarly journals Tyr198 is the Essential Autophosphorylation Site for STK16 Localization and Kinase Activity

2019 ◽  
Vol 20 (19) ◽  
pp. 4852 ◽  
Author(s):  
Junjun Wang ◽  
Juanjuan Liu ◽  
Xinmiao Ji ◽  
Xin Zhang
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Activity ◽  
Kinase Domain ◽  
Serine Threonine Kinase ◽  
Cycle Progression ◽  
Threonine Kinase ◽  
Cellular Processes ◽  
Activation Segment ◽  
And Function

STK16, reported as a Golgi localized serine/threonine kinase, has been shown to participate in multiple cellular processes, including the TGF-β signaling pathway, TGN protein secretion and sorting, as well as cell cycle and Golgi assembly regulation. However, the mechanisms of the regulation of its kinase activity remain underexplored. It was known that STK16 is autophosphorylated at Thr185, Ser197, and Tyr198 of the activation segment in its kinase domain. We found that STK16 localizes to the cell membrane and the Golgi throughout the cell cycle, but mutations in the auto-phosphorylation sites not only alter its subcellular localization but also affect its kinase activity. In particular, the Tyr198 mutation alone significantly reduced the kinase activity of STK16, abolished its Golgi and membrane localization, and affected the cell cycle progression. This study demonstrates that a single site autophosphorylation of STK16 could affect its localization and function, which provides insights into the molecular regulatory mechanism of STK16’s kinase activity.

scholarly journals Regulation of CDK7–Carboxyl-Terminal Domain Kinase Activity by the Tumor Suppressor p16INK4A Contributes to Cell Cycle Regulation

2000 ◽  
Vol 20 (20) ◽  
pp. 7726-7734 ◽  
Author(s):  
Eiji Nishiwaki ◽  
Saralinda L. Turner ◽  
Susanna Harju ◽  
Shiro Miyazaki ◽  
Masahide Kashiwagi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Tumor Suppressor ◽  
Rna Polymerase Ii ◽  
Cell Cycle Progression ◽  
Kinase Activity ◽  
Alternative Pathway ◽  
Cycle Progression ◽  
Terminal Domain ◽  
Carboxyl Terminal Domain ◽  
Carboxyl Terminal

ABSTRACT The eukaryotic cell cycle is regulated by cyclin-dependent kinases (CDKs). CDK4 and CDK6, which are activated by D-type cyclins during the G1 phase of the cell cycle, are thought to be responsible for phosphorylation of the retinoblastoma gene product (pRb). The tumor suppressor p16INK4A inhibits phosphorylation of pRb by CDK4 and CDK6 and can thereby block cell cycle progression at the G1/S boundary. Phosphorylation of the carboxyl-terminal domain (CTD) of the large subunit of RNA polymerase II by general transcription factor TFIIH is believed to be an important regulatory event in transcription. TFIIH contains a CDK7 kinase subunit and phosphorylates the CTD. We have previously shown that p16INK4A inhibits phosphorylation of the CTD by TFIIH. Here we report that the ability of p16INK4A to inhibit CDK7-CTD kinase contributes to the capacity to induce cell cycle arrest. These results suggest that p16INK4A may regulate cell cycle progression by inhibiting not only CDK4-pRb kinase activity but also by modulating CDK7-CTD kinase activity. Regulation of CDK7-CTD kinase activity by p16INK4A thus may represent an alternative pathway for controlling cell cycle progression.

Truncation in CCND1 mRNA 3′ UTR Is Associated with An Aggressive Phenotype and Chemoresistance

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5287-5287
Author(s):  
Robert W Chen ◽  
Myo Htut ◽  
Britta Hoehn ◽  
Eamon Berge ◽  
William Robinson ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Expression ◽  
Cyclin D1 ◽  
Cell Lines ◽  
Cell Cycle Progression ◽  
Serum Starvation ◽  
Cycle Progression ◽  
Serum Free ◽  
Aggressive Phenotype ◽  
Free Media

Abstract Mantle Cell Lymphoma (MCL) represents 5–10% of all non-Hodgkins lymphomas, making it an uncommon but difficult form of lymphoma to treat. It has the worst prognosis among the B cell lymphomas with median survival of three years. The genetic hallmark of MCL is the t(11,14)(q13;32) translocation causing amplification of cyclin D1 (CCND1). It is a well known cell cycle regulator. Multiple reports have shown a truncation in the cyclin D1 mRNA 3′ untranslated region. This truncation increases CCND1 protein expression by not only enhancing the half-life of CCND1 mRNA, but also evades microRNA regulation of mRNA translation. The dramatic overexpression of CCND1 mRNA and protein has been associated to poor clinical outcome in patients. We hypothesize that this truncation leads to a more aggressive phenotype and induces chemoresistance in MCL. We have identified 4 MCL cell lines (Granta-519, JVM-2, Jeko-1, and Z138) with different levels of the truncated CCND1 mRNA. We were able to show that Z138 and Jeko-1 have a much higher ratio of truncated CCND1 mRNA to the full length CCND1 mRNA as compared to Granta-519 and JVM-2. We were also able to show that this truncated mRNA leads to an increase in CCND1 protein expression. By using flow cytometry, we correlated the increase in CCND1 protein expression to faster cell cycle progression. We proposed that cell lines with increased CCND1 expression are phenotypically more aggressive, and would be able to continue cell cycle progression without serum support. We were able to arrest JVM-2 in G1 phase after 48 hours of serum starvation. However, we were not able to arrest cell cycle progression in Jeko-1 even after 96 hours of serum starvation. Western blot analysis shows that CCND1 protein expression is decreased in JVM-2 but remains unchanged in Jeko-1 with serum starvation. The same phenomenon was observed in Granta-519 and Z138. The MCL cell lines (Jeko-1 and Z-138) with more CCND1 protein expression were able to continue cell cycle progression in serum free media. The MCL cell lines (JVM-2 and Granta-519) with less CCND1 protein expression were not able to continue cell cycle progression in serum free media. This shows that CCND1 overexpression is associated with a more aggressive phenotype. We then treated the 4 MCL cell lines with varying concentrations of doxorubicin, a standard anthracycline chemotherapy used in the treatment of MCL patients. We used MTS assay to assess cell proliferation after treatment with doxorubicin. We found the IC 50 (inhibitory concentration 50%) of doxorubicin in these cell lines varied from 6nM to 600nM. The cell lines (Jeko-1 and Z-138) with more CCND1 protein expression have a much higher IC 50 as compared to the cell lines (JVM-2 and Granta-519) with less CCND1 protein expression. This demonstrates that CCND1 overexpression is associated with chemoresistance. We conclude truncation in CCND1 mRNA leads to increased CCND1 protein expression and faster cell cycle progression CCND1 overexpression is associated with an aggressive phenotype CCND1 overexpression is associated with chemoresistance.

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