Abstract
Polymerase-1 and release transcript factor (PTRF) was initially reported to be involved in the termination of the transcription process. More recently, it has been implicated in the formation of caveolae, cave-like structures in the plasma membrane. The effects of PTRF related to caveolae suggest that this protein may play important roles in health and disease. PTRF is highly expressed in various cells, including adipocytes, osteoblasts and muscle (cardiac, skeletal and smooth) cells. The role of PTRF in prostate cancer has been recently reviewed but there is growing evidence that PTRF is involved in other physiological processes such as cell repair and the regulation of glucose and lipid metabolism and, furthermore, altered expression of PTRF may be associated with disease. This review discusses the emerging role of PTRF in health and disease.
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References
Aboulaich N, Vainonen JP, Stralfors P, Vener AV (2004) Vectorial proteomics reveal targeting, phosphorylation and specific fragmentation of polymerase I and transcript release factor (PTRF) at the surface of caveolae in human adipocytes. Biochem J 383:237–248. doi:10.1042/bj20040647
Aboulaich N, Ortegren U, Vener AV, Stralfors P (2006) Association and insulin regulated translocation of hormone-sensitive lipase with PTRF. Biochem Biophys Res Commun 350:657–661. doi:10.1016/j.bbrc.2006.09.094
Aboulaich N, Chui PC, Asara JM, Flier JS, Maratos-Flier E (2011) Polymerase I and transcript release factor regulates lipolysis via a phosphorylation-dependent mechanism. Diabetes 60:757–765. doi:10.2337/db10-0744
Aung CS, Hill MM, Bastiani M, Parton RG, Parat MO (2011) PTRF-cavin-1 expression decreases the migration of PC3 prostate cancer cells: role of matrix metalloprotease 9. Eur J Cell Biol 90:136–142. doi:10.1016/j.ejcb.2010.06.004
Austin ED, Ma L, LeDuc C, Berman Rosenzweig E, Borczuk A, Phillips JA 3rd, Palomero T, Sumazin P, Kim HR, Talati MH, West J, Loyd JE, Chung WK (2012) Whole exome sequencing to identify a novel gene (caveolin-1) associated with human pulmonary arterial hypertension. Circ Cardiovasc Genet 5:336–343. doi:10.1161/circgenetics.111.961888
Badesch DB, Champion HC, Sanchez MA, Hoeper MM, Loyd JE, Manes A, McGoon M, Naeije R, Olschewski H, Oudiz RJ, Torbicki A (2009) Diagnosis and assessment of pulmonary arterial hypertension. J Am Coll Cardiol 54:S55–S66. doi:10.1016/j.jacc.2009.04.011
Bai L, Deng X, Li J, Wang M, Li Q, An W, Deli A, Cong YS (2011) Regulation of cellular senescence by the essential caveolar component PTRF/Cavin-1. Cell Res 21:1088–1101. doi:10.1038/cr.2011.56
Bai L, Deng X, Li Q, Wang M, An W, Deli A, Gao Z, Xie Y, Dai Y, Cong YS (2012) Down-regulation of the cavin family proteins in breast cancer. J Cell Biochem 113:322–328. doi:10.1002/jcb.23358
Bansal D, Miyake K, Vogel SS, Groh S, Chen CC, Williamson R, McNeil PL, Campbell KP (2003) Defective membrane repair in dysferlin-deficient muscular dystrophy. Nature 423:168–172. doi:10.1038/nature01573
Beausejour CM, Krtolica A, Galimi F, Narita M, Lowe SW, Yaswen P, Campisi J (2003) Reversal of human cellular senescence: roles of the p53 and p16 pathways. EMBO J 22:4212–4222. doi:10.1093/emboj/cdg417
Bitar MS, Abdel-Halim SM, Al-Mulla F (2013) Caveolin-1/PTRF upregulation constitutes a mechanism for mediating p53-induced cellular senescence: implications for evidence-based therapy of delayed wound healing in diabetes. Am J Physiol Endocrinol Metab 305:E951–E963. doi:10.1152/ajpendo.00189.2013
Cai C, Masumiya H, Weisleder N, Matsuda N, Nishi M, Hwang M, Ko JK, Lin P, Thornton A, Zhao X, Pan Z, Komazaki S, Brotto M, Takeshima H, Ma J (2009) MG53 nucleates assembly of cell membrane repair machinery. Nat Cell Biol 11:56–64. doi:10.1038/ncb1812
Cao CM, Zhang Y, Weisleder N, Ferrante C, Wang X, Lv F, Zhang Y, Song R, Hwang M, Jin L, Guo J, Peng W, Li G, Nishi M, Takeshima H, Ma J, Xiao RP (2010) MG53 constitutes a primary determinant of cardiac ischemic preconditioning. Circulation 121:2565–2574. doi:10.1161/circulationaha.110.954628
Cong YS, Fan E, Wang E (2006) Simultaneous proteomic profiling of four different growth states of human fibroblasts, using amine-reactive isobaric tagging reagents and tandem mass spectrometry. Mech Ageing Dev 127:332–343. doi:10.1016/j.mad.2005.12.005
Dwianingsih EK, Takeshima Y, Itoh K, Yamauchi Y, Awano H, Malueka RG, Nishida A, Ota M, Yagi M, Matsuo M (2010) A Japanese child with asymptomatic elevation of serum creatine kinase shows PTRF-CAVIN mutation matching with congenital generalized lipodystrophy type 4. Mol Genet Metab 101:233–237. doi:10.1016/j.ymgme.2010.06.016
Emery AE (2002) The muscular dystrophies. Lancet 359:687–695. doi:10.1016/s0140-6736(02)07815-7
Eren E, Ozkan TB, Cakir ED, Saglam H, Tarim O (2010) Acquired generalized lipodystrophy associated with autoimmune hepatitis and low serum C4 level. J Clin Res Pediatr Endocrinol 2:39–42. doi:10.4274/jcrpe.v2i1.39
Gamez-Pozo A, Sanchez-Navarro I, Calvo E, Agullo-Ortuno MT, Lopez-Vacas R, Diaz E, Camafeita E, Nistal M, Madero R, Espinosa E, Lopez JA, Fresno Vara JA (2012) PTRF/cavin-1 and MIF proteins are identified as non-small cell lung cancer biomarkers by label-free proteomics. PLoS ONE 7:e33752. doi:10.1371/journal.pone.0033752
Garg A (2004) Acquired and inherited lipodystrophies. N Engl J Med 350:1220–1234. doi:10.1056/NEJMra025261
Garg A, Agarwal AK (2009) Lipodystrophies: disorders of adipose tissue biology. Biochim Biophys Acta 1791:507–513. doi:10.1016/j.bbalip.2008.12.014
Gil J (1983) Number and distribution of plasmalemmal vesicles in the lung. Fed Proc 42:2414–2418
Glover L, Brown RH Jr (2007) Dysferlin in membrane trafficking and patch repair. Traffic 8:785–794. doi:10.1111/j.1600-0854.2007.00573.x
Gould ML, Williams G, Nicholson HD (2010) Changes in caveolae, caveolin, and polymerase 1 and transcript release factor (PTRF) expression in prostate cancer progression. Prostate 70:1609–1621. doi:10.1002/pros.21195
Govender P, Romero F, Shah D, Paez J, Ding SY, Liu L, Gower A, Baez E, Aly SS, Pilch P, Summer R (2013) Cavin1; a regulator of lung function and macrophage phenotype. PLoS ONE 8:e62045. doi:10.1371/journal.pone.0062045
Grummt I, Rosenbauer H, Niedermeyer I, Maier U, Ohrlein A (1986) A repeated 18 bp sequence motif in the mouse rDNA spacer mediates binding of a nuclear factor and transcription termination. Cell 45:837–846
Guha U, Chaerkady R, Marimuthu A, Patterson AS, Kashyap MK, Harsha HC, Sato M, Bader JS, Lash AE, Minna JD, Pandey A, Varmus HE (2008) Comparisons of tyrosine phosphorylated proteins in cells expressing lung cancer-specific alleles of EGFR and KRAS. Proc Natl Acad Sci U S A 105:14112–14117. doi:10.1073/pnas.0806158105
Hayashi YK, Matsuda C, Ogawa M, Goto K, Tominaga K, Mitsuhashi S, Park YE, Nonaka I, Hino-Fukuyo N, Haginoya K, Sugano H, Nishino I (2009) Human PTRF mutations cause secondary deficiency of caveolins resulting in muscular dystrophy with generalized lipodystrophy. J Clin Invest 119:2623–2633. doi:10.1172/jci38660
Hayflick L (1965) The limited in vitro lifetime of human diploid cell strains. Exp Cell Res 37:614–636
Hayflick L (1985) Theories of biological aging. Exp Gerontol 20:145–159
Heath D, Smith P (1979) The pulmonary endothelial cell. Thorax 34:200–208
Hermann M, Flammer A, Luscher TF (2006) Nitric oxide in hypertension. J Clin Hypertens (Greenwich Conn) 8:17–29
Hill MM, Bastiani M, Luetterforst R, Kirkham M, Kirkham A, Nixon SJ, Walser P, Abankwa D, Oorschot VM, Martin S, Hancock JF, Parton RG (2008) PTRF-Cavin, a conserved cytoplasmic protein required for caveola formation and function. Cell 132:113–124. doi:10.1016/j.cell.2007.11.042
Hill MM, Daud NH, Aung CS, Loo D, Martin S, Murphy S, Black DM, Barry R, Simpson F, Liu L, Pilch PF, Hancock JF, Parat MO, Parton RG (2012) Co-regulation of cell polarization and migration by caveolar proteins PTRF/Cavin-1 and caveolin-1. PLoS ONE 7:e43041. doi:10.1371/journal.pone.0043041
Hsu LL, Champion HC, Campbell-Lee SA, Bivalacqua TJ, Manci EA, Diwan BA, Schimel DM, Cochard AE, Wang X, Schechter AN, Noguchi CT, Gladwin MT (2007) Hemolysis in sickle cell mice causes pulmonary hypertension due to global impairment in nitric oxide bioavailability. Blood 109:3088–3098. doi:10.1182/blood-2006-08-039438
Inder KL, Zheng YZ, Davis MJ, Moon H, Loo D, Nguyen H, Clements JA, Parton RG, Foster LJ, Hill MM (2012) Expression of PTRF in PC-3 Cells modulates cholesterol dynamics and the actin cytoskeleton impacting secretion pathways. Mol Cell Proteomics 11(M111):012245. doi:10.1074/mcp.M111.012245
Jansa P, Grummt I (1999) Mechanism of transcription termination: PTRF interacts with the largest subunit of RNA polymerase I and dissociates paused transcription complexes from yeast and mouse. Mol Gen Genet 262:508–514
Jansa P, Mason SW, Hoffmann-Rohrer U, Grummt I (1998) Cloning and functional characterization of PTRF, a novel protein which induces dissociation of paused ternary transcription complexes. EMBO J 17:2855–2864. doi:10.1093/emboj/17.10.2855
Jansa P, Burek C, Sander EE, Grummt I (2001) The transcript release factor PTRF augments ribosomal gene transcription by facilitating reinitiation of RNA polymerase I. Nucleic Acids Res 29:423–429
Karbalaei MS, Rippe C, Albinsson S, Ekman M, Mansten A, Uvelius B, Sward K (2012) Impaired contractility and detrusor hypertrophy in cavin-1-deficient mice. Eur J Pharmacol 689:179–185. doi:10.1016/j.ejphar.2012.05.023
Liu L, Pilch PF (2008) A critical role of cavin (polymerase I and transcript release factor) in caveolae formation and organization. J Biol Chem 283:4314–4322. doi:10.1074/jbc.M707890200
Liu L, Brown D, McKee M, Lebrasseur NK, Yang D, Albrecht KH, Ravid K, Pilch PF (2008) Deletion of Cavin/PTRF causes global loss of caveolae, dyslipidemia, and glucose intolerance. Cell Metab 8:310–317. doi:10.1016/j.cmet.2008.07.008
Liu X, Fassett J, Wei Y, Chen Y (2013) Regulation of DDAH1 as a Potential Therapeutic Target for Treating Cardiovascular Diseases. Evid Based Complement Alternat Med 2013:619207. doi:10.1155/2013/619207
Machado RD, Eickelberg O, Elliott CG, Geraci MW, Hanaoka M, Loyd JE, Newman JH, Phillips JA 3rd, Soubrier F, Trembath RC, Chung WK (2009) Genetics and genomics of pulmonary arterial hypertension. J Am Coll Cardiol 54:S32–S42. doi:10.1016/j.jacc.2009.04.015
Maniatis NA, Shinin V, Schraufnagel DE, Okada S, Vogel SM, Malik AB, Minshall RD (2008) Increased pulmonary vascular resistance and defective pulmonary artery filling in caveolin-1−/− mice. Am J Physiol Lung Cell Mol Physiol 294:L865–L873. doi:10.1152/ajplung.00079.2007
Murakami N, Hayashi YK, Oto Y, Shiraishi M, Itabashi H, Kudo K, Nishino I, Nonaka I, Nagai T (2013) Congenital generalized lipodystrophy type 4 with muscular dystrophy: clinical and pathological manifestations in early childhood. Neuromuscul Disord 23:441–444. doi:10.1016/j.nmd.2013.02.005
Nassar ZD, Hill MM, Parton RG, Parat MO (2013a) Caveola-forming proteins caveolin-1 and PTRF in prostate cancer. Nat Rev Urol 10:529–536. doi:10.1038/nrurol.2013.168
Nassar ZD, Moon H, Duong T, Neo L, Hill MM, Francois M, Parton RG, Parat MO (2013b) PTRF/Cavin-1 decreases prostate cancer angiogenesis and lymphangiogenesis. Oncotarget 4:1844–1855
Ng Y, Ramm G, Lopez JA, James DE (2008) Rapid activation of Akt2 is sufficient to stimulate GLUT4 translocation in 3T3-L1 adipocytes. Cell Metab 7:348–356. doi:10.1016/j.cmet.2008.02.008
Ortegren U, Yin L, Ost A, Karlsson H, Nystrom FH, Stralfors P (2006) Separation and characterization of caveolae subclasses in the plasma membrane of primary adipocytes; segregation of specific proteins and functions. FEBS J 273:3381–3392. doi:10.1111/j.1742-4658.2006.05345.x
Ost A, Ortegren U, Gustavsson J, Nystrom FH, Stralfors P (2005) Triacylglycerol is synthesized in a specific subclass of caveolae in primary adipocytes. J Biol Chem 280:5–8. doi:10.1074/jbc.C400429200
Parton RG, del Pozo MA (2013) Caveolae as plasma membrane sensors, protectors and organizers. Nat Rev Mol Cell Biol 14:98–112. doi:10.1038/nrm3512
Pernow J, Jung C (2013) Arginase as a potential target in the treatment of cardiovascular disease: reversal of arginine steal? Cardiovasc Res 98:334–343. doi:10.1093/cvr/cvt036
Pilch PF (2008) The mass action hypothesis: formation of Glut4 storage vesicles, a tissue-specific, regulated exocytic compartment. Acta Physiol (Oxford, England) 192:89–101. doi:10.1111/j.1748-1716.2007.01788.x
Rajab A, Straub V, McCann LJ, Seelow D, Varon R, Barresi R, Schulze A, Lucke B, Lutzkendorf S, Karbasiyan M, Bachmann S, Spuler S, Schuelke M (2010) Fatal cardiac arrhythmia and long-QT syndrome in a new form of congenital generalized lipodystrophy with muscle rippling (CGL4) due to PTRF-CAVIN mutations. PLoS Genet 6:e1000874. doi:10.1371/journal.pgen.1000874
Shastry S, Delgado MR, Dirik E, Turkmen M, Agarwal AK, Garg A (2010) Congenital generalized lipodystrophy, type 4 (CGL4) associated with myopathy due to novel PTRF mutations. Am J Med Genet A 152A:2245–2253. doi:10.1002/ajmg.a.33578
Sward K, Sadegh MK, Mori M, Erjefalt JS, Rippe C (2013) Elevated pulmonary arterial pressure and altered expression of Ddah1 and Arg1 in mice lacking cavin-1/PTRF. Physiol Rep 1:e00008. doi:10.1002/phy2.8
Sward K, Albinsson S, Rippe C (2014) Arterial dysfunction but maintained systemic blood pressure in cavin-1-deficient mice. PLoS ONE 9:e92428. doi:10.1371/journal.pone.0092428
Verma P, Ostermeyer-Fay AG, Brown DA (2010) Caveolin-1 induces formation of membrane tubules that sense actomyosin tension and are inhibited by polymerase I and transcript release factor/cavin-1. Mol Biol Cell 21:2226–2240. doi:10.1091/mbc.E09-05-0417
Vinten J, Johnsen AH, Roepstorff P, Harpoth J, Tranum-Jensen J (2005) Identification of a major protein on the cytosolic face of caveolae. Biochim Biophys Acta 1717:34–40. doi:10.1016/j.bbamem.2005.09.013
Volonte D, Galbiati F (2011) Polymerase I and transcript release factor (PTRF)/cavin-1 is a novel regulator of stress-induced premature senescence. J Biol Chem 286:28657–28661. doi:10.1074/jbc.C111.235119
Wanaski SP, Ng BK, Glaser M (2003) Caveolin scaffolding region and the membrane binding region of SRC form lateral membrane domains. Biochemistry 42:42–56. doi:10.1021/bi012097n
Wang X, Xie W, Zhang Y, Lin P, Han L, Han P, Wang Y, Chen Z, Ji G, Zheng M, Weisleder N, Xiao RP, Takeshima H, Ma J, Cheng H (2010) Cardioprotection of ischemia/reperfusion injury by cholesterol-dependent MG53-mediated membrane repair. Circ Res 107:76–83. doi:10.1161/circresaha.109.215822
Williams JJ, Palmer TM (2014) Cavin-1: caveolae-dependent signalling and cardiovascular disease. Biochem Soc Trans 42:284–288. doi:10.1042/bst20130270
Yi JS, Mun DG, Lee H, Park JS, Lee JW, Lee JS, Kim SJ, Cho BR, Lee SW, Ko YG (2013) PTRF/cavin-1 is essential for multidrug resistance in cancer cells. J Proteome Res 12:605–614. doi:10.1021/pr300651m
Zheng Y, Lee S, Liang X, Wei S, Moon HG, Jin Y (2013) Suppression of PTRF alleviates the polymicrobial sepsis induced by cecal ligation and puncture in mice. J Infect Dis 208:1803–1812. doi:10.1093/infdis/jit364
Zhu H, Lin P, De G, Choi KH, Takeshima H, Weisleder N, Ma J (2011) Polymerase transcriptase release factor (PTRF) anchors MG53 protein to cell injury site for initiation of membrane repair. J Biol Chem 286:12820–12824. doi:10.1074/jbc.C111.221440
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We would like to thank Dr E Gold for critically reviewing the manuscript and the University of Otago for the Doctoral Scholarship awarded to Jin-Yih Low.
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Low, JY., Nicholson, H.D. Emerging role of polymerase-1 and transcript release factor (PTRF/ Cavin-1) in health and disease. Cell Tissue Res 357, 505–513 (2014). https://doi.org/10.1007/s00441-014-1964-z
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DOI: https://doi.org/10.1007/s00441-014-1964-z