Characterization of Protein Kinase chk1 Essential for the Cell Cycle Checkpoint after Exposure of Human Head and Neck Carcinoma A253 Cells to a Novel Topoisomerase I Inhibitor BNP1350

2000 ◽  
Vol 57 (3) ◽  
pp. 453-459 ◽  
Author(s):  
Ming-Biao Yin ◽  
Bin Guo ◽  
Udo Vanhoefer ◽  
Rami G. Azrak ◽  
Hans Minderman ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Head And Neck ◽  
Topoisomerase I ◽  
Head And Neck Carcinoma ◽  
Human Head ◽  
Cell Cycle Checkpoint ◽  
Neck Carcinoma ◽  
Cycle Checkpoint

scholarly journals Xenopus Cds1 Is Regulated by DNA-Dependent Protein Kinase and ATR during the Cell Cycle Checkpoint Response to Double-Stranded DNA Ends

2004 ◽  
Vol 24 (22) ◽  
pp. 9968-9985 ◽  
Author(s):  
Troy D. McSherry ◽  
Paul R. Mueller
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Cell Cycle Checkpoint ◽  
Dual Function ◽  
Dependent Protein Kinase ◽  
Double Stranded Dna ◽  
Cycle Checkpoint ◽  
Protein Dissociation ◽  
Dependent Protein ◽  
Dna Ends

ABSTRACT The checkpoint kinase Cds1 (Chk2) plays a key role in cell cycle checkpoint responses with functions in cell cycle arrest, DNA repair, and induction of apoptosis. Proper regulation of Cds1 is essential for appropriate cellular responses to checkpoint-inducing insults. While the kinase ATM has been shown to be important in the regulation of human Cds1 (hCds1), here we report that the kinases ATR and DNA-dependent protein kinase (DNA-PK) play more significant roles in the regulation of Xenopus Cds1 (XCds1). Under normal cell cycle conditions, nonactivated XCds1 constitutively associates with a Xenopus ATR complex. The association of XCds1 with this complex does not require a functional forkhead activation domain but does require a putative SH3 binding region that is found in XCds1. In response to double-stranded DNA ends, the amino terminus of XCds1 is rapidly phosphorylated in a sequential pattern. First DNA-PK phosphorylates serine 39, a site not previously recognized as important in Cds1 regulation. Xenopus ATM, ATR, and/or DNA-PK then phosphorylate three consensus serine/glutamine sites. Together, these phosphorylations have the dual function of inducing dissociation from the ATR complex and independently promoting the full activation of XCds1. Thus, the checkpoint-mediated activation of XCds1 requires phosphorylation by multiple phosphoinositide 3-kinase-related kinases, protein-protein dissociation, and autophosphorylation.

Abstract 1127: Aberrant nuclear expression of GSK-3beta in human head and neck carcinoma

2017 ◽  
Author(s):  
Maria Matsangou ◽  
Andrey Ugolkov ◽  
Timothy J. Taxter ◽  
Sandeep Samant ◽  
Andrew P. Mazar ◽  
...  
Keyword(s):  
Head And Neck ◽  
Head And Neck Carcinoma ◽  
Human Head ◽  
Nuclear Expression ◽  
Neck Carcinoma

scholarly journals Activity of the Vascular-Disrupting Agent 5,6-Dimethylxanthenone-4-Acetic Acid against Human Head and Neck Carcinoma Xenografts

Neoplasia ◽  
2006 ◽  
Vol 8 (7) ◽  
pp. 534-542 ◽  
Author(s):  
Mukund Seshadri ◽  
Richard Mazurchuk ◽  
Joseph A. Spernyak ◽  
Arup Bhattacharya ◽  
Youcef M. Rustum ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Head And Neck ◽  
Head And Neck Carcinoma ◽  
Human Head ◽  
Vascular Disrupting Agent ◽  
Neck Carcinoma ◽  
Vascular Disrupting

Identification and Characterization of a Paralog of Human Cell Cycle Checkpoint Gene HUS1

Genomics ◽  
2002 ◽  
Vol 79 (4) ◽  
pp. 487-492 ◽  
Author(s):  
Haiying Hang ◽  
Yuzhu Zhang ◽  
Roland L. Dunbrack ◽  
Cuidong Wang ◽  
Howard B. Lieberman
Keyword(s):  
Cell Cycle ◽  
Human Cell ◽  
Cell Cycle Checkpoint ◽  
Checkpoint Gene ◽  
Cycle Checkpoint ◽  
Identification And Characterization

scholarly journals Bortezomib sensitizes human head and neck carcinoma cells SQ20B to radiation

2007 ◽  
Vol 6 (2) ◽  
pp. 156-159 ◽  
Author(s):  
Charles N. Weber ◽  
George J. Cerniglia ◽  
Amit Maity ◽  
Anjali K. Gupta
Keyword(s):  
Head And Neck ◽  
Head And Neck Carcinoma ◽  
Human Head ◽  
Carcinoma Cells ◽  
Neck Carcinoma

scholarly journals Activation of Akt/Protein Kinase B Overcomes a G2/M Cell Cycle Checkpoint Induced by DNA Damage

2002 ◽  
Vol 22 (22) ◽  
pp. 7831-7841 ◽  
Author(s):  
Eugene S. Kandel ◽  
Jennifer Skeen ◽  
Nathan Majewski ◽  
Antonio Di Cristofano ◽  
Pier Paolo Pandolfi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Protein Kinase ◽  
Protein Kinase B ◽  
Es Cells ◽  
Cell Cycle Checkpoint ◽  
Wild Type ◽  
M Cell ◽  
Human Cancers ◽  
Cycle Checkpoint

ABSTRACT Activation of Akt, or protein kinase B, is frequently observed in human cancers. Here we report that Akt activation via overexpression of a constitutively active form or via the loss of PTEN can overcome a G2/M cell cycle checkpoint that is induced by DNA damage. Activated Akt also alleviates the reduction in CDC2 activity and mitotic index upon exposure to DNA damage. In addition, we found that PTEN null embryonic stem (ES) cells transit faster from the G2/M to the G1 phase of the cell cycle when compared to wild-type ES cells and that inhibition of phosphoinositol-3-kinase (PI3K) in HEK293 cells elicits G2 arrest that is alleviated by activated Akt. Furthermore, the transition from the G2/M to the G1 phase of the cell cycle in Akt1 null mouse embryo fibroblasts (MEFs) is attenuated when compared to that of wild-type MEFs. These results indicate that the PI3K/PTEN/Akt pathway plays a role in the regulation of G2/M transition. Thus, cells expressing activated Akt continue to divide, without being eliminated by apoptosis, in the presence of continuous exposure to mutagen and accumulate mutations, as measured by inactivation of an exogenously expressed herpes simplex virus thymidine kinase (HSV-tk) gene. This phenotype is independent of p53 status and cannot be reproduced by overexpression of Bcl-2 or Myc and Bcl-2 but seems to counteract a cell cycle checkpoint mediated by DNA mismatch repair (MMR). Accordingly, restoration of the G2/M cell cycle checkpoint and apoptosis in MMR-deficient cells, through reintroduction of the missing component of MMR, is alleviated by activated Akt. We suggest that this new activity of Akt in conjunction with its antiapoptotic activity may contribute to genetic instability and could explain its frequent activation in human cancers.

scholarly journals The Cell Cycle Checkpoint System MAST(L)-ENSA/ARPP19-PP2A is Targeted by cAMP/PKA and cGMP/PKG in Anucleate Human Platelets

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 472 ◽  
Author(s):  
Elena J. Kumm ◽  
Oliver Pagel ◽  
Stepan Gambaryan ◽  
Ulrich Walter ◽  
René P. Zahedi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Map Kinases ◽  
Human Platelets ◽  
Cell Cycle Checkpoint ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Proteomic Data ◽  
Cycle Checkpoint ◽  
Phosphatase 2A

The cell cycle is controlled by microtubule-associated serine/threonine kinase-like (MASTL), which phosphorylates the cAMP-regulated phosphoproteins 19 (ARPP19) at S62 and 19e/α-endosulfine (ENSA) at S67and converts them into protein phosphatase 2A (PP2A) inhibitors. Based on initial proteomic data, we hypothesized that the MASTL-ENSA/ARPP19-PP2A pathway, unknown until now in platelets, is regulated and functional in these anucleate cells. We detected ENSA, ARPP19 and various PP2A subunits (including seven different PP2A B-subunits) in proteomic studies of human platelets. ENSA-S109/ARPP19–S104 were efficiently phosphorylated in platelets treated with cAMP- (iloprost) and cGMP-elevating (NO donors/riociguat) agents. ENSA-S67/ARPP19-S62 phosphorylations increased following PP2A inhibition by okadaic acid (OA) in intact and lysed platelets indicating the presence of MASTL or a related protein kinase in human platelets. These data were validated with recombinant ENSA/ARPP19 and phospho-mutants using recombinant MASTL, protein kinase A and G. Both ARPP19 phosphorylation sites S62/S104 were dephosphorylated by platelet PP2A, but only S62-phosphorylated ARPP19 acted as PP2A inhibitor. Low-dose OA treatment of platelets caused PP2A inhibition, diminished thrombin-stimulated platelet aggregation and increased phosphorylation of distinct sites of VASP, Akt, p38 and ERK1/2 MAP kinases. In summary, our data establish the entire MASTL(like)–ENSA/ARPP19–PP2A pathway in human platelets and important interactions with the PKA, MAPK and PI3K/Akt systems.

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