Prohibitin-2 is a novel regulator of p21WAF1/CIP1 induced by depletion of γ-glutamylcyclotransferase

Taniguchi, Keiko; Matsumura, Kazuaki; Kageyama, Susumu; Hiromi,; Ashihara, Eishi; Chano, Tokuhiro; Kawauchi, Akihiro; Tokura, Y.; Nakata, Susumu

doi:10.1016/j.bbrc.2018.01.029

Cited by 12 publications

(13 citation statements)

References 27 publications

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“…We analyzed 109 MT-nDNA proteins using the PPI network (see Web Resources) 87,88 to identify 4,132 interacting proteins. We present the 15 top genes (Table S11) with highest PageRank score for PPI, [89][90][91] including the number of PPI, a short description of gene's function from Gene Entrez of NCBI-db, associated trait(s), and association p value(s) (see also Supplemental Material and Methods, section 9). From the PPI analysis it is evident that a gene/protein hub (which is assumed important because of a relatively large number of interactions) is not necessary, the topnotch for association with a specific trait, as shown in the Discussion section.…”

Section: Ppi Networkmentioning

confidence: 99%

Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits

Kraja¹,

Liu

Fetterman

et al. 2019

The American Journal of Human Genetics

109

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Mitochondria (MT), the major site of cellular energy production, are under dual genetic control by 37 mitochondrial DNA (mtDNA) genes and numerous nuclear genes (MT-nDNA). In the CHARGEmtDNAþ Consortium, we studied genetic associations of mtDNA and MT-nDNA associations with body mass index (BMI), waist-hip-ratio (WHR), glucose, insulin, HOMA-B, HOMA-IR, and HbA1c. This 45-cohort collaboration comprised 70,775 (insulin) to 170,202 (BMI) pan-ancestry individuals. Validation and imputation of mtDNA variants was followed by single-variant and gene-based association testing. We report two significant common variants, one in MT-ATP6 associated (p % 5EÀ04) with WHR and one in the D-loop with glucose. Five rare variants in MT-ATP6, MT-ND5, and MT-ND6 associated with BMI, WHR, or insulin. Gene-based meta-analysis identified MT-ND3 associated with BMI (p % 1EÀ03). We considered 2,282 MT-nDNA candidate gene associations compiled from online summary results for our traits (20 unique studies with 31 dataset consortia's genome-wide associations [GWASs]). Of these, 109 genes associated (p % 1EÀ06) with at least 1 of our 7 traits. We assessed regulatory features of variants in the 109 genes, cis-and trans-gene expression regulation, and performed enrichment and protein-protein interactions analyses. Of the identified mtDNA and MT-nDNA genes, 79 associated with adipose measures, 49 with glucose/insulin, 13 with risk for type 2 diabetes, and 18 with cardiovascular disease, indicating for pleiotropic effects with health implications. Additionally, 21 genes related to cholesterol, suggesting additional important roles for the genes identified. Our results suggest that mtDNA and MT-nDNA genes and variants reported make important contributions to glucose and insulin metabolism, adipocyte regulation, diabetes, and cardiovascular disease.

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Section: Ppi Networkmentioning

confidence: 99%

Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits

Kraja¹,

Liu

Fetterman

et al. 2019

The American Journal of Human Genetics

109

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“…Prohibitins are important intercellular communicators between the nucleus and mitochondria, and their many functions are highly dependent on their localization (270). Both prohibitins localize to the inner membrane, functioning as mitochondrial chaperones, although they are also present in the plasma membrane and nucleus where they act in membrane signaling and independently as transcriptional repressors of target genes, respectively (271)(272)(273). As regards the implication of PHB2 in transcription, Zhou et al recently described its substantial localization in the nucleolus, where it maintains nucleolar morphology, while promoting tumor proliferation and probably repressing differentiation in rhabdomyosarcoma cells (273).…”

Section: Mitochondrion and Nucleusmentioning

confidence: 99%

Biomarkers of tumor invasiveness in proteomics (Review)

et al. 2020

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Over the past two decades, quantitative proteomics has emerged as an important tool for deciphering the complex molecular events involved in cancers. The number of references involving studies on the cancer metastatic process has doubled since 2010, while the last 5 years have seen the development of novel technologies combining deep proteome coverage capabilities with quantitative consistency and accuracy. To highlight key findings within this huge amount of information, the present review identified a list of tumor invasive biomarkers based on both the literature and data collected on a biocollection of experimental cell lines, tumor models of increasing invasiveness and tumor samples from patients with colorectal or breast cancer. Crossing these different data sources led to 76 proteins of interest out of 1,245 mentioned in the literature. Information on these proteins can potentially be translated into clinical prospects, since they represent potential targets for the development and evaluation of innovative therapies, alone or in combination. Herein, a systematical review of the biology of each of these proteins, including their specific subcellular/extracellular or multiple localizations is presented. Finally, as an important advantage of quantitative proteomics is the ability to provide data on all these molecules simultaneously in cell pellets, body fluids or paraffin-embedded sections of tumors/invaded tissues, the significance of some of their interconnections is discussed.

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“…Proteins binding to GGCT have been discovered only recently. To identify proteins interacting with GGCT, Taniguchi et al performed yeast two-hybrid screening and found that the PHB2 protein bound to GGCT, a result also confirmed by the immunoprecipitation of MCF7 cell lysates using an anti-GGCT monoclonal antibody [ 29 ]. They also showed that nuclear expression of PHB2 in MCF7 cells was decreased after GGCT knockdown, and that overexpression of PHB2 inhibited p21 upregulation, caused by GGCT knockdown.…”

Section: Intracellular Changes Caused By Ggct Depletionmentioning

confidence: 99%

Mechanisms of Tumor Growth Inhibition by Depletion of γ-Glutamylcyclotransferase (GGCT): A Novel Molecular Target for Anticancer Therapy

Kageyama

Hiromi

Taniguchi

et al. 2018

IJMS

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γ-Glutamylcyclotransferase (GGCT), which is one of the major enzymes involved in glutathione metabolism, is upregulated in a wide range of cancers—glioma, breast, lung, esophageal, gastric, colorectal, urinary bladder, prostate, cervical, ovarian cancers and osteosarcoma—and promotes cancer progression; its depletion leads to the suppression of proliferation, invasion, and migration of cancer cells. It has been demonstrated that the suppression or inhibition of GGCT has an antitumor effect in cancer-bearing xenograft mice. Based on these observations, GGCT is now recognized as a promising therapeutic target in various cancers. This review summarizes recent advances on the mechanisms of the antitumor activity of GGCT inhibition.

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Prohibitin-2 is a novel regulator of p21WAF1/CIP1 induced by depletion of γ-glutamylcyclotransferase

Cited by 12 publications

References 27 publications

Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits

Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits

Biomarkers of tumor invasiveness in proteomics (Review)

Mechanisms of Tumor Growth Inhibition by Depletion of γ-Glutamylcyclotransferase (GGCT): A Novel Molecular Target for Anticancer Therapy

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