International Journal of Gerontology
Volume 2, Issue 4 , Pages 158-166 , December 2008

Beyond Oncogenesis: The Role of S-Phase Kinase-Associated Protein-2 (SKP2) In Vascular Restenosis

  • Yih-Jer Wu

      Affiliations

    • Cardiovascular Medicine and Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
    • Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan
    • Corresponding Author InformationCorrespondence to: Dr Yih-Jer Wu, Cardiovascular Medicine, Mackay Memorial Hospital, 92, Section 2, Chung Shan North Road, Taipei 10449, Taiwan
    • ,
  • Hung-I Yeh

      Affiliations

    • Cardiovascular Medicine and Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
    • Mackay Medicine, Nursing and Management College and Taipei Medical University, Taipei, Taiwan
    • ,
  • Charles Jia-Yin Hou

      Affiliations

    • Cardiovascular Medicine and Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
    • ,
  • Cheng-Ho Tsai

      Affiliations

    • Cardiovascular Medicine and Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
    • Mackay Medicine, Nursing and Management College and Taipei Medical University, Taipei, Taiwan
    • ,
  • Andrew C. Newby

      Affiliations

    • Bristol Heart Institute, University of Bristol, Bristol, United Kingdom
    • ,
  • Mark Bond

      Affiliations

    • Bristol Heart Institute, University of Bristol, Bristol, United Kingdom

,Accepted 20 September 2008.

References 

  1. Smith SC , Dove JT , Jacobs AK , Kennedy JW , Kereiakes D , Kern MJ , et al.   ACC/AHA guidelines of percutaneous coronary interventions (revision of the 1993 PTCA guidelines)—executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (committee to revise the 1993 guidelines for percutaneous transluminal coronary angioplasty) . J Am Coll Cardiol . 2001;37:2215–2239
  2. Poon M , Badimon JJ , Fuster V . Overcoming restenosis with sirolimus: from alphabet soup to clinical reality . Lancet . 2002;359:619–622
  3. Welt FG , Rogers C . Inflammation and restenosis in the stent era . Arterioscler Thromb Vasc Biol . 2002;22:1769–1776
  4. Braun-Dullaeus RC , Mann MJ , Dzau VJ . Cell cycle progression: new therapeutic target for vascular proliferative disease . Circulation . 1998;98:82–89
  5. Dzau VJ , Braun-Dullaeus RC , Sedding DG . Vascular proliferation and atherosclerosis: new perspectives and therapeutic strategies . Nat Med . 2002;8:1249–1256
  6. Gershlick AH . Treating atherosclerosis: local drug delivery from laboratory studies to clinical trials . Atherosclerosis . 2002;160:259–271
  7. Newby AC , Zaltsman AB . Molecular mechanisms in intimal hyperplasia . J Pathol . 2000;190:300–309
  8. Costa MA , Simon DI . Molecular basis of restenosis and drug-eluting stents . Circulation . 2005;111:2257–2273
  9. Sriram V , Patterson C . Cell cycle in vasculoproliferative diseases: potential interventions and routes of delivery . Circulation . 2001;103:2414–2419
  10. Morice MC , Serruys PW , Sousa JE , Fajadet J , Ban Hayashi E , Perin M , et al.   A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization . N Engl J Med . 2002;346:1773–1780
  11. Park SJ , Shim WH , Ho DS , Raizner AE , Park SW , Hong MK , et al.   A paclitaxel-eluting stent for the prevention of coronary restenosis . N Engl J Med . 2003;348:1537–1545
  12. Spencer CM , Faulds D . Paclitaxel. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the treatment of cancer . Drugs . 1994;48:794–847
  13. Chan S . Targeting the mammalian target of rapamycin (mTOR): a new approach to treating cancer . Br J Cancer . 2004;91:1420–1424
  14. Le XF , Hittelman WN , Liu J , McWatters A , Li C , Mills GB , et al.   Paclitaxel induces inactivation of p70 S6 kinase and phosphorylation of Thr421 and Ser424 via multiple signaling pathways in mitosis . Oncogene . 2003;22:484–497
  15. Joner M , Finn AV , Farb A , Mont EK , Kolodgie FD , Ladich E , et al.   Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk . J Am Coll Cardiol . 2006;48:193–202
  16. Luscher TF , Steffel J , Eberli FR , Joner M , Nakazawa G , Tanner FC , et al.   Drug-eluting stent and coronary thrombosis: biological mechanisms and clinical implications . Circulation . 2007;115:1051–1058
  17. Finn AV , Joner M , Nakazawa G , Kolodgie F , Newell J , John MC , et al.   Pathological correlates of late drugeluting stent thrombosis: strut coverage as a marker of endothelialization . Circulation . 2007;115:2435–2441
  18. Finn AV , Nakazawa G , Joner M , Kolodgie FD , Mont EK , Gold HK , et al.   Vascular responses to drug eluting stents: importance of delayed healing . Arterioscler Thromb Vasc Biol . 2007;27:1500–1510
  19. Nigg EA . Cyclin-dependent protein kinases: key regulators of the eukaryotic cell cycle . Bioessays . 1995;17:471–480
  20. Koepp DM , Harper JW , Elledge SJ . How the cyclin became a cyclin: regulated proteolysis in the cell cycle . Cell . 1999;97:431–434
  21. Ohtsubo M , Theodoras AM , Schumacher J , Roberts JM , Pagano M . Human cyclin E, a nuclear protein essential for the G1-to-S phase transition . Mol Cell Biol . 1995;15:2612–2624
  22. Sclafani RA . Cyclin dependent kinase activating kinases . Curr Opin Cell Biol . 1996;8:788–794
  23. Toyoshima H , Hunter T . p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21 . Cell . 1994;78:67–74
  24. Harper JW , Adami GR , Wei N , Keyomarsi K , Elledge SJ . The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases . Cell . 1993;75:805–816
  25. Lee MH , Reynisdottir I , Massague J . Cloning of p57KIP2, a cyclin-dependent kinase inhibitor with unique domain structure and tissue distribution . Genes Dev . 1995;9:639–649
  26. Koff A , Ohtsuki M , Polyak K , Roberts JM , Massague J . Negative regulation of G1 in mammalian cells: inhibition of cyclin E-dependent kinase by TGF-beta . Science . 1993;260:536–539
  27. Polyak K , Kato JY , Solomon MJ , Sherr CJ , Massague J , Roberts JM , et al.   p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest . Genes Dev . 1994;8:9–22
  28. Hulleman E , Boonstra J . Regulation of G1 phase progression by growth factors and the extracellular matrix . Cell Mol Life Sci . 2001;58:80–93
  29. Zhu X , Ohtsubo M , Bohmer RM , Roberts JM , Assoian RK . Adhesion-dependent cell cycle progression linked to the expression of cyclin D1, activation of cyclin E-cdk2, and phosphorylation of the retinoblastoma protein . J Cell Biol . 1996;133:391–403
  30. Nakayama K , Nagahama H , Minamishima YA , Miyake S , Ishida N , Hatakeyama S , et al.   Skp2-mediated degradation of p27 regulates progression into mitosis . Dev Cell . 2004;6:661–672
  31. Kossatz U , Dietrich N , Zender L , Buer J , Manns MP , Malek NP . Skp2-dependent degradation of p27kip1 is essential for cell cycle progression . Genes Dev . 2004;18:2602–2607
  32. Pagano M . Control of DNA synthesis and mitosis by the Skp2-p27-Cdk1/2 axis . Mol Cell . 2004;14:414–416
  33. Hengst L , Reed SI . Translational control of p27Kip1 accumulation during the cell cycle . Science . 1996;271:1861–1864
  34. Bloom J , Pagano M . Deregulated degradation of the cdk inhibitor p27 and malignant transformation . Semin Cancer Biol . 2003;13:41–47
  35. Pagano M , Tam SW , Theodoras AM , Beer-Romero P , Del Sal G , Chau V , et al.   Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27 . Science . 1995;269:682–685
  36. King RW , Deshaies RJ , Peters JM , Kirschner MW . How proteolysis drives the cell cycle . Science . 1996;274:1652–1659
  37. Reed SI . Ratchets and clocks: the cell cycle, ubiquitylation and protein turnover . Nat Rev Mol Cell Biol . 2003;4:855–864
  38. Zachariae W , Nasmyth K . Whose end is destruction: cell division and the anaphase-promoting complex . Genes Dev . 1999;13:2039–2058
  39. Hershko A , Ciechanover A . Mechanisms of intracellular protein breakdown . Annu Rev Biochem . 1982;51:335–364
  40. Nakayama KI , Hatakeyama S , Nakayama K . Regulation of the cell cycle at the G1-S transition by proteolysis of cyclin E and p27Kip1 . Biochem Biophys Res Commun . 2001;282:853–860
  41. Nalepa G , Wade Harper J . Therapeutic anti-cancer targets upstream of the proteasome . Cancer Treat Rev . 2003;29:49–57
  42. Zheng N , Schulman BA , Song L , Miller JJ , Jeffrey PD , Wang P , et al.   Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex . Nature . 2002;416:703–709
  43. Skowyra D , Craig KL , Tyers M , Elledge SJ , Harper JW . F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex . Cell . 1997;91:209–219
  44. Carrano AC , Eytan E , Hershko A , Pagano M . SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27 . Nat Cell Biol . 1999;1:193–199
  45. Sutterluty H , Chatelain E , Marti A , Wirbelauer C , Senften M , Muller U , et al.   p45SKP2 promotes p27Kip1 degradation and induces S phase in quiescent cells . Nat Cell Biol . 1999;1:207–214
  46. Yu ZK , Gervais JL , Zhang H . Human CUL-1 associates with the SKP1/SKP2 complex and regulates p21CIP1/WAF1 and cyclin D proteins . Proc Natl Acad Sci USA . 1998;95:11324–11329
  47. Bornstein G , Bloom J , Sitry-Shevah D , Nakayama K , Pagano M , Hershko A . Role of the SCFSkp2 ubiquitin ligase in the degradation of p21Cip1 in S phase . J Biol Chem . 2003;278:25752–25757
  48. Kamura T , Hara T , Kotoshiba S , Yada M , Ishida N , Imaki H , et al.   Degradation of p57Kip2 mediated by SCFSkp2dependent ubiquitylation . Proc Natl Acad Sci USA . 2003;100:10231–10236
  49. Nakayama K , Nagahama H , Minamishima YA , Matsumoto M , Nakamichi I , Kitagawa K , et al.   Targeted disruption of Skp2 results in accumulation of cyclin E and p27Kip1, polyploidy and centrosome overduplication . EMBO J . 2000;19:2069–2081
  50. Huang H , Regan KM , Wang F , Wang D , Smith DI , van Deursen JM , et al.   Skp2 inhibits FOXO1 in tumor suppression through ubiquitin-mediated degradation . Proc Natl Acad Sci USA . 2005;102:1649–1654
  51. Lin YW , Yang JL . Cooperation of ERK and SCFSkp2 for MKP-1 destruction provides a positive feedback regulation of proliferating signaling . J Biol Chem . 2006;281:915–926
  52. Gstaiger M , Jordan R , Lim M , Catzavelos C , Mestan J , Slingerland J , et al.   Skp2 is oncogenic and overexpressed in human cancers . Proc Natl Acad Sci USA . 2001;98:5043–5048
  53. Latres E , Chiarle R , Schulman BA , Pavletich NP , Pellicer A , Inghirami G , et al.   Role of the F-box protein Skp2 in lymphomagenesis . Proc Natl Acad Sci USA . 2001;98:2515–2520
  54. Signoretti S , Di Marcotullio L , Richardson A , Ramaswamy S , Isaac B , Rue M , et al.   Oncogenic role of the ubiquitin ligase subunit Skp2 in human breast cancer . J Clin Invest . 2002;110:633–641
  55. Dong Y , Sui L , Watanabe Y , Sugimoto K , Tokuda M . S-phase kinase-associated protein 2 expression in laryngeal squamous cell carcinomas and its prognostic implications . Oncol Rep . 2003;10:321–325
  56. Kudo Y , Kitajima S , Sato S , Miyauchi M , Ogawa I , Takata T . High expression of S-phase kinase-interacting protein 2, human F-box protein, correlates with poor prognosis in oral squamous cell carcinomas . Cancer Res . 2001;61:7044–7047
  57. Li JQ , Wu F , Masaki T , Kubo A , Fujita J , Dixon DA , et al.   Correlation of Skp2 with carcinogenesis, invasion, metastasis, and prognosis in colorectal tumors . Int J Oncol . 2004;25:87–95
  58. Masuda TA , Inoue H , Sonoda H , Mine S , Yoshikawa Y , Nakayama K , et al.   Clinical and biological significance of S-phase kinase-associated protein 2 (Skp2) gene expression in gastric carcinoma: modulation of malignant phenotype by Skp2 overexpression, possibly via p27 proteolysis . Cancer Res . 2002;62:3819–3825
  59. Min YH , Cheong JW , Lee MH , Kim JY , Lee ST , Hahn JS , et al.   Elevated S-phase kinase-associated protein 2 protein expression in acute myelogenous leukemia: its association with constitutive phosphorylation of phosphatase and tensin homologue protein and poor prognosis . Clin Cancer Res . 2004;10:5123–5130
  60. Penin RM , Fernandez-Figueras MT , Puig L , Rex J , Ferrandiz C , Ariza A . Over-expression of p45SKP2 in Kaposi's sarcoma correlates with higher tumor stage and extracutaneous involvement but is not directly related to p27KIP1 down-regulation . Mod Pathol . 2002;15:1227–1235
  61. Shigemasa K , Gu L , O'Brien TJ , Ohama K . Skp2 overexpression is a prognostic factor in patients with ovarian adenocarcinoma . Clin Cancer Res . 2003;9:1756–1763
  62. Shintani S , Li C , Mihara M , Hino S , Nakashiro K , Hamakawa H . Skp2 and Jab1 expression are associated with inverse expression of p27KIP1 and poor prognosis in oral squamous cell carcinomas . Oncology . 2003;65:355–362
  63. Yokoi S , Yasui K , Mori M , Iizasa T , Fujisawa T , Inazawa J . Amplification and overexpression of SKP2 are associated with metastasis of non-small-cell lung cancers to lymph nodes . Am J Pathol . 2004;165:175–180
  64. Zhu CQ , Blackhall FH , Pintilie M , Iyengar P , Liu N , Ho J , et al.   Skp2 gene copy number aberrations are common in non-small cell lung carcinoma, and its overexpression in tumors with ras mutation is a poor prognostic marker . Clin Cancer Res . 2004;10:1984–1991
  65. Carrano AC , Pagano M . Role of the F-box protein Skp2 in adhesion-dependent cell cycle progression . J Cell Biol . 2001;153:1381–1390
  66. Shim EH , Johnson L , Noh HL , Kim YJ , Sun H , Zeiss C , et al.   Expression of the F-box protein SKP2 induces hyperplasia, dysplasia, and low-grade carcinoma in the mouse prostate . Cancer Res . 2003;63:1583–1588
  67. Mehran R , Mintz GS , Popma JJ , Pichard AD , Satler LF , Kent KM , et al.   Mechanisms and results of balloon angioplasty for the treatment of in-stent restenosis . Am J Cardiol . 1996;78:618–622
  68. Bennett MR , O'Sullivan M . Mechanisms of angioplasty and stent restenosis: implications for design of rational therapy . Pharmacol Ther . 2001;91:149–166
  69. Bond M , Sala-Newby GB , Newby AC . Focal adhesion kinase (FAK)-dependent regulation of S-phase kinaseassociated protein-2 (Skp-2) stability. A novel mechanism regulating smooth muscle cell proliferation . J Biol Chem . 2004;279:37304–37310
  70. Bond M , Sala-Newby GB , Wu YJ , Newby AC . Biphasic effect of p21Cip1 on smooth muscle cell proliferation: role of PI 3-kinase and Skp2-mediated degradation . Cardiovasc Res . 2006;69:198–206
  71. Wu YJ , Bond M , Sala-Newby GB , Newby AC . Altered S-phase kinase-associated protein-2 levels are a major mediator of cyclic nucleotide-induced inhibition of vascular smooth muscle cell proliferation . Circ Res . 2006;98:1141–1150
  72. Schwartz SM , Campbell GR , Campbell JH . Replication of smooth muscle cells in vascular disease . Circ Res . 1986;58:427–444
  73. Izzard TD , Taylor C , Birkett SD , Jackson CL , Newby AC . Mechanisms underlying maintenance of smooth muscle cell quiescence in rat aorta: role of the cyclin dependent kinases and their inhibitors . Cardiovasc Res . 2002;53:242–252
  74. Thyberg J . Phenotypic modulation of smooth muscle cells during formation of neointimal thickenings following vascular injury . Histol Histopathol . 1998;13:871–891
  75. Tanner FC , Yang ZY , Duckers E , Gordon D , Nabel GJ , Nabel EG . Expression of cyclin-dependent kinase inhibitors in vascular disease . Circ Res . 1998;82:396–403
  76. Wu YJ , Newby AC , Sala-Newby GB , Bond M . S-phase kinase-associated protein-2, a key player in smooth muscle cell proliferation and intimal thickening in vitro and in vivo . Circulation . 2005;112(Suppl):II–71
  77. Wu YJ , Newby AC , Sala-Newby GB , Hsu KT , Tseng S , Lin YC , et al.   The role of S-phase kinase-associated protein-2 (Skp2) in the regulation of vascular smooth muscle cell migration and apoptosis in vitro and neointimal thickening in vivo . Int J Cardiol . 2007;122:S48
  78. Stoker M , O'Neill C , Berryman S , Waxman V . Anchorage and growth regulation in normal and virus-transformed cells . Int J Cancer . 1968;3:683–693
  79. Giancotti FG , Ruoslahti E . Integrin signaling . Science . 1999;285:1028–1032
  80. Wu YJ . The role of S-phase kinase-associated protein 2 in regulation of vascular smooth muscle cell proliferation [PhD thesis] . Bristol: Bristol Heart Institute, University of Bristol; 2006;
  81. Ross R , Glomset JA . The pathogenesis of atherosclerosis (first of two parts) . N Engl J Med . 1976;295:369–377
  82. Lindner V , Lappi DA , Baird A , Majack RA , Reidy MA . Role of basic fibroblast growth factor in vascular lesion formation . Circ Res . 1991;68:106–113
  83. Shirotani M , Yui Y , Hattori R , Kawai C . U-61,431F, a stable prostacyclin analogue, inhibits the proliferation of bovine vascular smooth muscle cells with little antiproliferative effect on endothelial cells . Prostaglandins . 1991;41:97–110
  84. Newby AC , Southgate KM , Assender JW . Inhibition of vascular smooth muscle cell proliferation by endotheliumdependent vasodilators . Herz . 1992;17:291–299
  85. Jeremy JY , Rowe D , Emsley AM , Newby AC . Nitric oxide and the proliferation of vascular smooth muscle cells . Cardiovasc Res . 1999;43:580–594
  86. Garg UC , Hassid A . Nitric oxide-generating vasodilators and 8-bromo-cyclic guanosine monophosphate inhibit mitogenesis and proliferation of cultured rat vascular smooth muscle cells . J Clin Invest . 1989;83:1774–1777
  87. Pelletier S , Julien C , Popoff MR , Lamarche-Vane N , Meloche S . Cyclic AMP induces morphological changes of vascular smooth muscle cells by inhibiting a racdependent signaling pathway . J Cell Physiol . 2005;204:412–422
  88. Matozaki T , Nakanishi H , Takai Y . Small G-protein networks: their crosstalk and signal cascades . Cell Signal . 2000;12:515–524
  89. Bond M , Wu YJ , Sala-Newby GB , Newby AC . Rho GTPase, Rac1, regulates Skp2 levels, vascular smooth muscle cell proliferation, and intima formation in vitro and in vivo . Cardiovasc Res . 2008;80:290–298
  90. Sakai T , Sakaue H , Nakamura T , Okada M , Matsuki Y , Watanabe E , et al.   Skp2 controls adipocyte proliferation during the development of obesity . J Biol Chem . 2007;282:2038–2046
  91. Bryant P , Zheng Q , Pumiglia K . Focal adhesion kinase controls cellular levels of p27/Kip1 and p21/Cip1 through Skp2-dependent and -independent mechanisms . Mol Cell Biol . 2006;26:4201–4213
  92. Gillis C , Jonzon B , Haegerstrand A . Effects of sera, basic fibroblast growth factor, heparin and cyclic AMPstimulation on proliferation of human vascular endothelial cells . Cell Mol Biol (Noisy-le-grand) . 1995;41:1131–1138
  93. Fantidis P , Fernandez-Ortiz A , Aragoncillo P , Perez De Prada T , Sanmartin M , Lopez J , et al.   [Effect of cAMP on the function of endothelial cells and fibromuscular proliferation after the injury of the carotid and coronary arteries in a porcine model.] . Rev Esp Cardiol . 2001;54:981–989 [In Spanish]
  94. Davison PM , Karasek MA . Human dermal microvascular endothelial cells in vitro: effect of cyclic AMP on cellular morphology and proliferation rate . J Cell Physiol . 1981;106:253–258

PII: S1873-9598(09)70004-3

doi: 10.1016/S1873-9598(09)70004-3

International Journal of Gerontology
Volume 2, Issue 4 , Pages 158-166 , December 2008

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