Glucose Metabolism and Carcinogenesis: The Impact of the Tumor Suppressor p53

The tumor suppressor p53 is a transcriptional factor broadly mutated in cancer. Most inactivating and gain of function mutations disrupt the sequence-specific DNA binding domain, which activates target genes. This is perhaps the main reason why most research has focused on the relevance of such transcriptional activity for the prevention or elimination of cancer cells. Notwithstanding, transcriptional regulation may not be the only mechanism underlying its role in tumor suppression and therapeutic responses. In the past, a direct role of p53 in DNA repair transactions that include the regulation of homologous recombination has been suggested. More recently, the localization of p53 at replication forks has been demonstrated and the effect of p53 on nascent DNA elongation has been explored. While some data sets indicate that the regulation of ongoing replication forks by p53 may be mediated by p53 targets such as MDM2 (murine double minute 2) and polymerase (POL) eta other evidences demonstrate that p53 is capable of controlling DNA replication by directly interacting with the replisome and altering its composition. In addition to discussing such findings, this review will also analyze the impact that p53-mediated control of ongoing DNA replication has on treatment responses and tumor suppressor abilities of this important anti-oncogene.

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Faculty Opinions recommendation of The tumor suppressor p53 limits ferroptosis by blocking DPP4 activity.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.728766256.793539127 ◽

2017 ◽

Author(s):

Ygal Haupt ◽

Sue Haupt

Keyword(s):

Tumor Suppressor ◽

Tumor Suppressor P53

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Interaction of the Tumor Suppressor p53 With Replication Protein A.

10.21236/ada366910 ◽

1998 ◽

Author(s):

Anindya Dutta

Keyword(s):

Tumor Suppressor ◽

Protein A ◽

Replication Protein A ◽

Replication Protein ◽

Tumor Suppressor P53

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Regulation of the Activity and Stability of the Tumor Suppressor p53 In Vivo

10.21236/ada403430 ◽

2001 ◽

Author(s):

Yang Xo

Keyword(s):

Tumor Suppressor ◽

Tumor Suppressor P53

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Breast Tumor Kinetics in Mice Overexpressing Cyclin E and Heterozygous for Tumor Suppressor p53 or Rb

10.21236/ada416982 ◽

2003 ◽

Author(s):

Adrian P. Smith ◽

Steven I. Reed ◽

John A. Lee

Keyword(s):

Tumor Suppressor ◽

Breast Tumor ◽

Cyclin E ◽

Tumor Suppressor P53 ◽

Tumor Kinetics

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Dense Liquid Condensates Host the Nucleation of Tumor Suppressor p53 Fibrils

SSRN Electronic Journal ◽

10.2139/ssrn.3249470 ◽

2018 ◽

Author(s):

Mohammad S. Safari ◽

Zhiqing Wang ◽

Kunaal Tailor ◽

Anatoly B. Kolomeisky ◽

Jacinta C. Conrad ◽

...

Keyword(s):

Tumor Suppressor ◽

Tumor Suppressor P53 ◽

Dense Liquid

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The Sumoylation Modulated Tumor Suppressor p53 Regulates Cell Cycle Checking Genes to Mediate Lens Differentiation

Current Molecular Medicine ◽

10.2174/1566524019666190111154450 ◽

2019 ◽

Vol 18 (8) ◽

pp. 556-565 ◽

Cited By ~ 1

Author(s):

Xiangcheng Tang ◽

Zhigang Chen ◽

Mi Deng ◽

Ling Wang ◽

Qian Nie ◽

...

Keyword(s):

Cell Cycle ◽

Tumor Suppressor ◽

Tumor Suppressor P53

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The impact of a multi-domain intervention on cerebral glucose metabolism: analysis from the randomized ancillary FDG PET MAPT trial

Alzheimer s Research & Therapy ◽

10.1186/s13195-020-00683-6 ◽

2020 ◽

Vol 12 (1) ◽

Author(s):

Julien Delrieu ◽

Thierry Voisin ◽

Laure Saint-Aubert ◽

Isabelle Carrie ◽

Christelle Cantet ◽

...

Keyword(s):

Glucose Metabolism ◽

Fdg Pet ◽

Primary Outcome ◽

Cognitive Stimulation ◽

Cerebral Glucose Metabolism ◽

Parahippocampal Gyrus ◽

Cerebral Magnetic Resonance Imaging ◽

Brain Glucose ◽

Brain Glucose Metabolism ◽

The Impact

Abstract Background The Multidomain Alzheimer Preventive Trial (MAPT) was designed to assess the efficacy of omega-3 fatty acid supplementation, multidomain intervention (MI), or a combination of both on cognition. Although the MAPT study was negative, an effect of MI in maintaining cognitive functions compared to placebo group was showed in positive amyloid subjects. A FDG PET study (MAPT-NI) was implemented to test the impact of MI on brain glucose metabolism. Methods MAPT-NI was a randomized, controlled parallel-group single-center study, exploring the effect of MI on brain glucose metabolism. Participants were non-demented and had memory complaints, limitation in one instrumental activity of daily living, or slow gait. Participants were randomly assigned (1:1) to “MI group” or “No MI group.” The MI consisted of group sessions focusing on 3 domains: cognitive stimulation, physical activity, nutrition, and a preventive consultation. [18F]FDG PET scans were performed at baseline, 6 months, and 12 months, and cerebral magnetic resonance imaging scans at baseline. The primary objective was to evaluate the MI effect on brain glucose metabolism assessed by [18F]FDG PET imaging at 6 months. The primary outcome was the quantification of regional metabolism rate for glucose in cerebral regions involved early in Alzheimer disease by relative semi-quantitative SUVr (FDG-based AD biomarker). An exploratory voxel-wise analysis was performed to assess the effect of MI on brain glucose metabolism without anatomical hypothesis. Results The intention-to-treat population included 67 subjects (34 in the MI group and 33 in the No MI group. No significant MI effect was observed on primary outcome at 6 months. In the exploratory voxel-wise analysis, we observed a difference in favor of MI group on the change of cerebral glucose metabolism in limbic lobe (right hippocampus, right posterior cingulate, left posterior parahippocampal gyrus) at 6 months. Conclusions MI failed to show an effect on metabolism in FDG-based AD biomarker, but exploratory analysis suggested positive effect on limbic system metabolism. This finding could suggest a delay effect of MI on AD progression. Trial registration ClinicalTrials.gov Identifier, NCT01513252.

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Impact of Glucose Metabolism Disorders on IGF-1 Levels in Patients with Acromegaly

Hormone and Metabolic Research ◽

10.1055/a-0594-2404 ◽

2018 ◽

Vol 50 (05) ◽

pp. 408-413 ◽

Cited By ~ 1

Author(s):

Sema Dogansen ◽

Gulsah Yalin ◽

Seher Tanrikulu ◽

Sema Yarman

Keyword(s):

Diabetes Mellitus ◽

Insulin Resistance ◽

Glucose Metabolism ◽

Glucose Tolerance ◽

Normal Glucose Tolerance ◽

Glucose Metabolism Disorders ◽

Insulin Resistant ◽

Normal Glucose ◽

Resistant Group ◽

The Impact

AbstractIn this study, we aimed to evaluate the presence of glucose metabolism abnormalities and their impact on IGF-1 levels in patients with acromegaly. Ninety-three patients with acromegaly (n=93; 52 males/41 females) were included in this study. Patients were separated into three groups such as; normal glucose tolerance (n=23, 25%), prediabetes (n=38, 41%), and diabetes mellitus (n=32, 34%). Insulin resistance was calculated with homeostasis model assessment (HOMA). HOMA-IR > 2.5 or ≤2.5 were defined as insulin resistant or noninsulin resistant groups, respectively. Groups were compared in terms of factors that may be associated with glucose metabolism abnormalities. IGF-1% ULN (upper limit of normal)/GH ratios were used to evaluate the impact of glucose metabolism abnormalities on IGF-1 levels. Patients with diabetes mellitus were significantly older with an increased frequency of hypertension (p<0.001, p=0.01, respectively). IGF-1% ULN/GH ratio was significantly lower in prediabetes group than in normal glucose tolerance group (p=0.04). Similarly IGF-1% ULN/GH ratio was significantly lower in insulin resistant group than in noninsulin resistant group (p=0.04). Baseline and suppressed GH levels were significantly higher in insulin resistant group than in noninsulin resistant group (p=0.024, p<0.001, respectively). IGF-1% ULN/GH ratio is a useful marker indicating glucose metabolism disorders and IGF-1 levels might be inappropriately lower in acromegalic patients with insulin resistance or prediabetes. We suggest that IGF-1 levels should be re-evaluated after the improvement of insulin resistance or glycemic regulation for the successful management of patients with acromegaly.

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