Isolation of a cDNA that hybrid selects antiproliferative mRNA from rat liver

Jk, McClung; Danner, David B.; Stewart, David A.; Smith, James R.; Schneider, Edward L.; Lumpkin, Charles K.; Dell’Orco, Robert T.; Nuell, Mark J.

doi:10.1016/0006-291x(89)91813-5

Cited by 150 publications

(115 citation statements)

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“…Greater knowledge of the pathway linking stimulation of the AR to cell growth is therefore vital in our drive to find new treatments for prostate cancer. In a study to find proteins regulated by exposure to androgens, we identified prohibitin, a protein with a possible role in cell-cycle control (McClung et al, 1989) that also shows sequence similarity to a known coregulator of the oestrogen receptor, REA (Nijtmans et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Prohibitin was initially suspected to be a tumour suppressor gene, due to the ability of the mRNA to inhibit DNA synthesis and cell cycle (McClung et al, 1989). Current data show two likely roles for the protein, firstly as a mitochondrial chaperone protein in a complex with BaP37/REA (Repressor of oEstrogen receptor Activity) (Coates et al, 1997), and secondly as a regulator of cell cycle (Nuell et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

“…The cell-cycle function of prohibitin is less well understood and there is some dispute over the precise role of the protein (Coates et al, 2001). Injection of the mRNA results in cell-cycle arrest in some cell types (McClung et al, 1989;Nuell et al, 1991), and this may in part be due to the 3 0 untranslated region (3 0 UTR) of the mRNA (Jupe et al, 1996). Even the localization of the protein is not clear, with some groups maintaining that the protein is purely mitochondrial (Coates et al, 2001), and others demonstrating a secondary localization in the nucleus (Thompson et al, 2001;Wang et al, 2002b).…”

Section: Introductionmentioning

confidence: 99%

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Androgens target prohibitin to regulate proliferation of prostate cancer cells

et al. 2004

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Proteins involved in the growth response of prostate cancer cells to androgen were investigated by comparing the proteomes of LNCaP cells treated with vehicle or androgen. Whole-cell lysates were separated by twodimensional PAGE, and HPLC-MS/MS was used to identify androgen-regulated proteins. Prohibitin, a protein with cell-cycle regulatory activity, was shown to be downregulated by 50% following androgen stimulation. Western blot and reverse transcription-PCR experiments confirmed the result and showed that regulation occurs at the level of transcription. To determine the importance of prohibitin in androgen-stimulated growth, we used transient transfection to overexpress the protein and RNA interference to knock down the protein. Subsequent FACS analysis showed that cells with reduced levels of prohibitin showed a slight but reproducible increase in the percentage of population in cell cycle, while cells with increased prohibitin levels showed a clear reduction in the percentage entering cell cycle, following dihydrotestosterone stimulation, when compared to untransfected controls. Confocal microscopy showed localization of prohibitin in the nucleus as well as the mitochondria of LNCaP cells. It therefore seems that the regulation of prohibitin is a vital part of the cellular growth response to androgen stimulation in LNCaPs and prohibitin may have a nuclear regulatory role in cell-cycle progression.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Androgens target prohibitin to regulate proliferation of prostate cancer cells

et al. 2004

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“…McClung et al [1] cloned it as one of the cDNAs derived from mRNAs which were more highly expressed in nondividing than regenerating rat liver ceils. The antiproliferative activity of prohibitin could be demonstrated by microinjection of the synthetic mRNA into normal fibroblasts and HeLa cells where it blocked the entry of cells into S phase [2].…”

Section: Introductionmentioning

confidence: 99%

Prohibitin, an antiproliferative protein, is localized to mitochondria

et al. 1995

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Prohibitin is a ubiquitously expressed protein with antiproliferative properties. When rat prohibitin tagged with a carboxy-terminal c-Myc epitope was expressed in baby hamster kidney cells the protein was targeted to mitochondria. In immunofluorescence microscopy prohibitin colocalized with a mitochondrial marker E3. lmmunoelectron microscopy revealed that prohibitin was associated with the periphery of mitochondria. The amino-terminus of prohibitin shares characteristics of the known mitochondrial import signals, and positioning of the tag at the N-terminus causes accumulation of the protein in the cytoplasm. These findings help to direct functional studies on prohibitin and suggest that a mitochondrial protein may act as a tumor suppressor.

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“…PHB1 was originally cloned from regenerating livers where its expression was nearly absent shortly after two-thirds partial hepatectomy and hence thought to be a tumor suppressor (11). To examine molecular mechanisms of action of Phb1 in the liver, we previously developed the liver-specific Phb1 knockout (Phb1 KO) mouse model (12).…”

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confidence: 99%

Prohibitin 1 Regulates the H19-Igf2 Axis and Proliferation in Hepatocytes

Ramani

Mavila

et al. 2016

Journal of Biological Chemistry

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Edited by Xiao-Fan WangProhibitin 1 (PHB1) is a mitochondrial chaperone that regulates cell growth. Phb1 knock-out mice exhibit liver injury and hepatocellular carcinoma (HCC). Phb1 knock-out livers show induction of tumor growth-associated genes, H19 and insulinlike growth factor 2 (Igf2). These genes are controlled by the imprinting control region (ICR) containing CCCTC-binding transcription factor (CTCF)-binding sites. Because Phb1 knockout mice exhibited induction of H19 and Igf2, we hypothesized that PHB1-mediated regulation of the H19-Igf2 axis might control cell proliferation in normal hepatocytes. H19 and Igf2 were induced (8 -20-fold) in 3-week-old Phb1 knock-out livers, in Phb1 siRNA-treated AML12 hepatocytes (2-fold), and HCC cell lines when compared with control. Phb1 knockdown lowered CTCF protein in AML12 by ϳ30% when compared with control. CTCF overexpression lowered basal H19 and Igf2 expression by 30% and suppressed Phb1 knockdown-mediated induction of these genes. CTCF and PHB1 co-immunoprecipitated and colocalized on the ICR element, and Phb1 knockdown lowered CTCF ICR binding activity. The results suggest that PHB1 and CTCF cooperation may control the H19-Igf2 axis. Human HCC tissues with high levels of H19 and IGF2 exhibited a 40 -50% reduction in PHB1 and CTCF expression and their ICR binding activity. Silencing Phb1 or overexpressing H19 in the mouse HCC cell line, SAMe-D, induced cell growth. Blocking H19 induction prevented Phb1 knockdown-mediated growth, whereas H19 overexpression had the reverse effect. Interestingly H19 silencing induced PHB1 expression. Taken together, our results demonstrate that the H19-Igf2 axis is negatively regulated by CTCF-PHB1 cooperation and that H19 is involved in modulating the growthsuppressive effect of PHB1 in the liver.

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Isolation of a cDNA that hybrid selects antiproliferative mRNA from rat liver

Cited by 150 publications

References 16 publications

Androgens target prohibitin to regulate proliferation of prostate cancer cells

Androgens target prohibitin to regulate proliferation of prostate cancer cells

Prohibitin, an antiproliferative protein, is localized to mitochondria

Prohibitin 1 Regulates the H19-Igf2 Axis and Proliferation in Hepatocytes

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