Induction of Paclitaxel Resistance by ERα Mediated Prohibitin Mitochondrial-Nuclear Shuttling

Dong, Pei; Jiang, Lijuan; Liu, Jianye; Wu, Zhiming; Guo, Shengjie; Zhang, Ziling; Zhou, Fangjian; Liu, Zhuowei

doi:10.1371/journal.pone.0083519

Cited by 18 publications

(23 citation statements)

References 35 publications

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“…However, a similar effect of PHB manipulation in adipocytes in vitro and in vivo (4,(8)(9)(10) suggests that the phenotype we have observed is most likely due to the role of PHB in adipocytes. PHB translocates from mitochondria to the nucleus in response to estrogen (17). In addition, PHB has been associated with the function of Tfam and nuclear factorlike 2 (Nrf-2) (18,19).…”

Section: Discussionmentioning

confidence: 99%

Prohibitin Overexpression in Adipocytes Induces Mitochondrial Biogenesis, Leads to Obesity Development, and Affects Glucose Homeostasis in a Sex-Specific Manner

et al. 2014

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Adipocytes are the primary cells in the body that store excess energy as triglycerides. To perform this specialized function, adipocytes rely on their mitochondria; however, the role of adipocyte mitochondria in the regulation of adipose tissue homeostasis and its impact on metabolic regulation is not understood. We developed a transgenic mouse model, Mito-Ob, overexpressing prohibitin (PHB) in adipocytes. Mito-Ob mice developed obesity due to upregulation of mitochondrial biogenesis in adipocytes. Of note, Mito-Ob female mice developed more visceral fat than male mice. However, female mice exhibited no change in glucose homeostasis and had normal insulin and high adiponectin levels, whereas male mice had impaired glucose homeostasis, compromised brown adipose tissue structure, and high insulin and low adiponectin levels. Mechanistically, we found that PHB overexpression enhances the cross talk between the mitochondria and the nucleus and facilitates mitochondrial biogenesis. The data suggest a critical role of PHB and adipocyte mitochondria in adipose tissue homeostasis and reveal sex differences in the effect of PHB-induced adipocyte mitochondrial remodeling on whole-body metabolism. Targeting adipocyte mitochondria may provide new therapeutic opportunities for the treatment of obesity, a major risk factor for type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

Prohibitin Overexpression in Adipocytes Induces Mitochondrial Biogenesis, Leads to Obesity Development, and Affects Glucose Homeostasis in a Sex-Specific Manner

et al. 2014

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“…2 ). In androgen-independent prostate cancer cells, estrogen activates ERα and promotes mitochondrial-nuclear PHB1 translocation, leading to cancer cell resistance to paclitaxel [ 52 ]. However, the translocation of PHB1 from the cytoplasm to the nucleus is also closely related to other apoptotic events.…”

Section: Phb and Nuclear Trafficking And Apoptosismentioning

confidence: 99%

Multifaceted role of prohibitin in cell survival and apoptosis

et al. 2015

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Human eukaryotic prohibitin (prohibitin-1 and prohibitin-2) is a membrane protein with different cellular localizations. It is involved in multiple cellular functions, including energy metabolism, proliferation, apoptosis, and senescence. The subcellular localization of prohibitin may determine its functions. Membrane prohibitin regulate the cellular signaling of membrane transport, nuclear prohibitin control transcription activation and the cell cycle, and mitochondrial prohibitin complex stabilize the mitochondrial genome and modulate mitochondrial dynamics, mitochondrial morphology, mitochondrial biogenesis, and the mitochondrial intrinsic apoptotic pathway. Moreover, prohibitin can translocates into the nucleus or the mitochondria under apoptotic signals and the subcellular shuttling of prohibitin is necessary for apoptosis process. Apoptosis is the process of programmed cell death that is important for the maintenance of normal physiological functions. Consequently, any alteration in the content, post-transcriptional modification (i.e. phosphorylation) or the nuclear or mitochondrial translocation of prohibitin may influence cell fate. Understanding the mechanisms of the expression and regulation of prohibitin may be useful for future research. This review provides an overview of the multifaceted and essential roles played by prohibitin in the regulation of cell survival and apoptosis.

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“… 14 , 15 These findings are in striking contrast to the previously proposed antiproliferative role of PHB and the predicted function as a negative regulator of E2F-mediated transcription, 10 , 11 though the difference in localization of PHB may explain the discrepancy. PHB has been visualized in the mitochondria, 16 , 17 nucleus 11 , 18 , 19 and plasma membrane 20 , 21 in different mammalian cell lines, although the exact role of PHB in each location remains unclear.…”

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confidence: 99%

Akt phosphorylates Prohibitin 1 to mediate its mitochondrial localization and promote proliferation of bladder cancer cells

et al. 2015

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Bladder cancer (BC) is very common and associated with significant morbidity and mortality, though the molecular underpinnings of its origination and progression remain poorly understood. In this study, we demonstrate that Prohibitin 1 (PHB) was overexpressed in human BC tissues and that PHB upregulation was associated with poor prognosis. We also found that PHB was necessary and sufficient for BC cell proliferation. Interestingly, the overexpressed PHB was primarily found within mitochondria, and we provide the first direct evidence that phosphorylation by Akt at Thr258 of PHB induces this mitochondrial localization. Inhibiton of Akt reverses these effects and inhibited the proliferation of BC cells. Finally, the phosphorylation of PHB was required for BC cell proliferation, further implicating the importance of the Akt in BC. Taken together, these findings identify the Akt/PHB signaling cascade as a novel mechanism of cancer cell proliferation and provide the scientific basis for the establishment of PHB as a new prognostic marker and treatment target for BC.

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Induction of Paclitaxel Resistance by ERα Mediated Prohibitin Mitochondrial-Nuclear Shuttling

Cited by 18 publications

References 35 publications

Prohibitin Overexpression in Adipocytes Induces Mitochondrial Biogenesis, Leads to Obesity Development, and Affects Glucose Homeostasis in a Sex-Specific Manner

Prohibitin Overexpression in Adipocytes Induces Mitochondrial Biogenesis, Leads to Obesity Development, and Affects Glucose Homeostasis in a Sex-Specific Manner

Multifaceted role of prohibitin in cell survival and apoptosis

Akt phosphorylates Prohibitin 1 to mediate its mitochondrial localization and promote proliferation of bladder cancer cells

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