scholarly journals MAPK mediated cell cycle regulation is associated with Cdc25 turnover inS. pombeafter exposure to genotoxic stress

Cell Cycle ◽  
2008 ◽  
Vol 7 (3) ◽  
pp. 365-372 ◽  
Author(s):  
Geetanjali Sundaram ◽  
Santanu Palchaudhuri ◽  
Swati Dixit ◽  
Dhrubajyoti Chattopadhyay
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulation ◽  
Genotoxic Stress ◽  
Cycle Regulation

scholarly journals A novel CDC25A/DYRK2 regulatory switch modulates cell cycle and survival

2021 ◽  
Author(s):  
Maribel Lara-Chica ◽  
Alejandro Correa-Sáez ◽  
Rafael Jiménez-Izquierdo ◽  
Martín Garrido-Rodríguez ◽  
Francisco J. Ponce ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Regulation ◽  
Cell Cycle Progression ◽  
Inverse Correlation ◽  
Genotoxic Stress ◽  
Cycle Progression ◽  
Relevant Effect ◽  
Regulatory Loop ◽  
Cycle Regulation

AbstractThe cell division cycle 25A (CDC25A) phosphatase is a key regulator of cell cycle progression that acts on the phosphorylation status of Cyclin–Cyclin-dependent kinase complexes, with an emergent role in the DNA damage response and cell survival control. The regulation of CDC25A activity and its protein level is essential to control the cell cycle and maintain genomic integrity. Here we describe a novel ubiquitin/proteasome-mediated pathway negatively regulating CDC25A stability, dependent on its phosphorylation by the serine/threonine kinase DYRK2. DYRK2 phosphorylates CDC25A on at least 7 residues, resulting in its degradation independent of the known CDC25A E3 ubiquitin ligases. CDC25A in turn is able to control the phosphorylation of DYRK2 at several residues outside from its activation loop, thus affecting DYRK2 localization and activity. An inverse correlation between DYRK2 and CDC25A protein amounts was observed during cell cycle progression and in response to DNA damage, with CDC25A accumulation responding to the manipulation of DYRK2 levels or activity in either physiological scenario. Functional data show that the pro-survival activity of CDC25A and the pro-apoptotic activity of DYRK2 could be partly explained by the mutual regulation between both proteins. Moreover, DYRK2 modulation of CDC25A expression and/or activity contributes to the DYRK2 role in cell cycle regulation. Altogether, we provide evidence suggesting that DYRK2 and CDC25A mutually control their activity and stability by a feedback regulatory loop, with a relevant effect on the genotoxic stress pathway, apoptosis, and cell cycle regulation.

scholarly journals Inhibition of TFII-I-Dependent Cell Cycle Regulation by p53

2005 ◽  
Vol 25 (24) ◽  
pp. 10940-10952 ◽  
Author(s):  
Zana P. Desgranges ◽  
Jinwoo Ahn ◽  
Maria B. Lazebnik ◽  
Todd Ashworth ◽  
Caleb Lee ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cyclin D1 ◽  
Cell Cycle Arrest ◽  
Cell Cycle Regulation ◽  
Cellular Proliferation ◽  
Cell Cycle Control ◽  
Genotoxic Stress ◽  
Dependent Manner ◽  
Cycle Arrest ◽  
Cycle Regulation

ABSTRACT The multifunctional transcription factor TFII-I is tyrosine phosphorylated in response to extracellular growth signals and transcriptionally activates growth-promoting genes. However, whether activation of TFII-I also directly affects the cell cycle profile is unknown. Here we show that under normal growth conditions, TFII-I is recruited to the cyclin D1 promoter and transcriptionally activates this gene. Most strikingly, upon cell cycle arrest resulting from genotoxic stress and p53 activation, TFII-I is ubiquitinated and targeted for proteasomal degradation in a p53- and ATM (ataxia telangiectasia mutated)-dependent manner. Consistent with a direct role of TFII-I in cell cycle regulation and cellular proliferation, stable and ectopic expression of wild-type TFII-I increases cyclin D1 levels, resulting in accelerated entry to and exit from S phase, and overcomes p53-mediated cell cycle arrest, despite radiation. We further show that the transcriptional regulation of cyclin D1 and cell cycle control by TFII-I are dependent on its tyrosine phosphorylation at positions 248 and 611, sites required for its growth signal-mediated transcriptional activity. Taken together, our data define TFII-I as a growth signal-dependent transcriptional activator that is critical for cell cycle control and proliferation and further reveal that genotoxic stress-induced degradation of TFII-I results in cell cycle arrest.

scholarly journals Genetic variants and cognitive functions in patients with brain tumors

2019 ◽  
Vol 21 (10) ◽  
pp. 1297-1309 ◽  
Author(s):  
Denise D Correa ◽  
Jaya Satagopan ◽  
Axel Martin ◽  
Erica Braun ◽  
Maria Kryza-Lacombe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Dna Repair ◽  
Brain Tumor ◽  
Brain Tumors ◽  
Cell Cycle Regulation ◽  
Cognitive Outcome ◽  
Cholesterol Transport ◽  
Tumor Patients ◽  
Cycle Regulation

AbstractBackgroundPatients with brain tumors treated with radiotherapy (RT) and chemotherapy (CT) often experience cognitive dysfunction. We reported that single nucleotide polymorphisms (SNPs) in the APOE, COMT, and BDNF genes may influence cognition in brain tumor patients. In this study, we assessed whether genes associated with late-onset Alzheimer’s disease (LOAD), inflammation, cholesterol transport, dopamine and myelin regulation, and DNA repair may influence cognitive outcome in this population.MethodsOne hundred and fifty brain tumor patients treated with RT ± CT or CT alone completed a neurocognitive assessment and provided a blood sample for genotyping. We genotyped genes/SNPs in these pathways: (i) LOAD risk/inflammation/cholesterol transport, (ii) dopamine regulation, (iii) myelin regulation, (iv) DNA repair, (v) blood–brain barrier disruption, (vi) cell cycle regulation, and (vii) response to oxidative stress. White matter (WM) abnormalities were rated on brain MRIs.ResultsMultivariable linear regression analysis with Bayesian shrinkage estimation of SNP effects, adjusting for relevant demographic, disease, and treatment variables, indicated strong associations (posterior association summary [PAS] ≥ 0.95) among tests of attention, executive functions, and memory and 33 SNPs in genes involved in: LOAD/inflammation/cholesterol transport (eg, PDE7A, IL-6), dopamine regulation (eg, DRD1, COMT), myelin repair (eg, TCF4), DNA repair (eg, RAD51), cell cycle regulation (eg, SESN1), and response to oxidative stress (eg, GSTP1). The SNPs were not significantly associated with WM abnormalities.ConclusionThis novel study suggests that polymorphisms in genes involved in aging and inflammation, dopamine, myelin and cell cycle regulation, and DNA repair and response to oxidative stress may be associated with cognitive outcome in patients with brain tumors.

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