Редактирование: PHB (раздел)

==Publications==

{{medline-entry
|title=Ubiquinol-cytochrome C reductase core protein II promotes tumorigenesis by facilitating p53 degradation.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30674441
|abstract=Ubiquinol-cytochrome C reductase core protein II (QCR2) is essential for mitochondrial functions, yet, its role in cancer development has remained elusive. The expression of QCR2 in cancer patients was assessed by immunohistochemistry. The proliferation of cancer cells was assessed by [[CCK]]-8 assay, EdU staining and Flow cytometry analysis. The biological function of QCR2 and [[PHB]] were determined using western blotting, RT-qPCR, microarray analysis and xenografts. The interactions between proteins and the ubiquitination of p53 were assessed by immunoprecipitation, mass spectrometry analysis and GST pull down. The subcellular location of [[PHB]] and QCR2 was assessed by immunoblotting and immunofluorescence. The expression of QCR2 is upregulated in multiple human tumors. Suppression of QCR2 inhibits cancer cell growth by activating p53 signaling and inducing p21-dependent cell cycle arrest and senescence. QCR2 directly interacts with [[PHB]] in the mitochondria. Overexpression of QCR2 inhibits [[PHB]] binding to p53 in the nucleus, and facilitates p53 ubiquitination and degradation, consequently leading to tumorigenesis. Also, increased QCR2 and decreased [[PHB]] protein levels are well correlated with decreased expression of p21 in cervical cancer tissues. These results identify a novel role for QCR2, together with [[PHB]], in negative regulation of p53 stability and activity, thus promote cervical carcinogenesis. FUND: "973" Program of China, the National Science-technology Supporting Plan Projects, the National Natural Science Foundation of China, National Science and Technology Major Sub-Project and Technical Innovation Special Project of Hubei Province.
|mesh-terms=* Animals
* Cell Cycle Checkpoints
* Cell Line, Tumor
* Cell Proliferation
* Cell Transformation, Neoplastic
* Cellular Senescence
* Electron Transport Complex III
* Female
* Gene Expression
* Gene Knockdown Techniques
* Gene Silencing
* Humans
* Immunohistochemistry
* Mice
* Models, Biological
* Neoplasms
* Protein Binding
* Proteolysis
* Tumor Suppressor Protein p53
* Ubiquitination
|keywords=* Degradation
* PHB
* QCR2
* Senescence
* Tumorigenesis
* p53
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412871
}}
{{medline-entry
|title=Analysis of the effect of the mitochondrial prohibitin complex, a context-dependent modulator of longevity, on the C. elegans metabolome.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26092086
|abstract=The mitochondrial prohibitin complex, composed of two proteins, [[PHB]]-1 and [[PHB]]-2, is a context-dependent modulator of longevity. Specifically, prohibitin deficiency shortens the lifespan of otherwise wild type worms, while it dramatically extends the lifespan under compromised metabolic conditions. This extremely intriguingly phenotype has been linked to alterations in mitochondrial function and in fat metabolism. However, the true function of the mitochondrial prohibitin complex remains elusive. Here, we used gas chromatography coupled to a flame ionization detector (GC/FID) and ¹H NMR spectroscopy to gain molecular insights into the effect of prohibitin depletion on the Caenorhabditis elegans metabolome. We analysed the effect of prohibitin deficiency in two different developmental stages and under two different conditions, which result in opposing longevity phenotypes, namely wild type worms and daf-2(e1370) insulin signalling deficient mutants. Prohibitin depletion was shown to alter the fatty acid (GC/FID) and ¹H NMR metabolic profiles of wild type animals both at the fourth larval stage of development (L4) and at the young adult (YA) stage, while being more pronounced at the later stage. Furthermore, wild type and the diapause mutant daf-2(e1370), either expressing or not prohibitin, were clearly distinguishable based on their metabolic profiles, revealing changes in fatty acid composition, as well as in carbohydrate and amino acid metabolism. Moreover, the metabolic data indicate that daf-2(e1370) mutants are more robust than the wild type animals to changes induced by prohibitin depletion. The impact of prohibitin depletion on the C. elegans metabolome will be discussed herein in the scope of its effect on longevity. This article is part of a Special Issue entitled: Mitochondrial Dysfunction in Aging. Guest Editor: Aleksandra Trifunovic.
|mesh-terms=* Animals
* Caenorhabditis elegans
* Fatty Acids
* Longevity
* Magnetic Resonance Spectroscopy
* Metabolome
* Mitochondria
* Repressor Proteins
|keywords=* C. elegans
* Insulin signalling
* Longevity
* Metabolomics
* Mitochondria
* Prohibitin
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580209
}}
{{medline-entry
|title=Prohibitin-mediated lifespan and mitochondrial stress implicate SGK-1, insulin/IGF and mTORC2 in C. elegans.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25265021
|abstract=Lifespan regulation by mitochondrial proteins has been well described, however, the mechanism of this regulation is not fully understood. Amongst the mitochondrial proteins profoundly affecting ageing are prohibitins ([[PHB]]-1 and [[PHB]]-2). Paradoxically, in C. elegans prohibitin depletion shortens the lifespan of wild type animals while dramatically extending that of metabolically compromised animals, such as daf-2-insulin-receptor mutants. Here we show that amongst the three kinases known to act downstream of daf-2, only loss of function of sgk-1 recapitulates the ageing phenotype observed in daf-2 mutants upon prohibitin depletion. Interestingly, signalling through SGK-1 receives input from an additional pathway, parallel to DAF-2, for the prohibitin-mediated lifespan phenotype. We investigated the effect of prohibitin depletion on the mitochondrial unfolded protein response (UPRmt). Remarkably, the lifespan extension upon prohibitin elimination, of both daf-2 and sgk-1 mutants, is accompanied by suppression of the UPRmt induced by lack of prohibitin. On the contrary, gain of function of SGK-1 results in further shortening of lifespan and a further increase of the UPRmt in prohibitin depleted animals. Moreover, SGK-1 interacts with RICT-1 for the regulation of the UPRmt in a parallel pathway to DAF-2. Interestingly, prohibitin depletion in rict-1 loss of function mutant animals also causes lifespan extension. Finally, we reveal an unprecedented role for mTORC2-SGK-1 in the regulation of mitochodrial homeostasis. Together, these results give further insight into the mechanism of lifespan regulation by mitochondrial function and reveal a cross-talk of mitochondria with two key pathways, Insulin/IGF and mTORC2, for the regulation of ageing and stress response. 
|mesh-terms=* Animals
* Caenorhabditis elegans
* Caenorhabditis elegans Proteins
* Insulin
* Life Expectancy
* Mechanistic Target of Rapamycin Complex 2
* Mitochondria
* Multiprotein Complexes
* Protein-Serine-Threonine Kinases
* Repressor Proteins
* Somatomedins
* Stress, Physiological
* TOR Serine-Threonine Kinases

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180437
}}