Clinical and Experimental Nephrology

, Volume 16, Issue 4, pp 507–517 | Cite as

The role of the ubiquitin–proteasome system in kidney diseases

Review Article

Abstract

Proteins in mammalian cells are continually being degraded and synthesized. Protein degradation via the ubiquitin–proteasome system (UPS) is the major pathway for non-lysosomal proteolysis of intracellular proteins and plays important roles in a variety of fundamental cellular processes such as regulation of cell cycle progression, differentiation, apoptosis, sodium channel function, and modulation of inflammatory responses. The central element of this system is the covalent linkage of ubiquitins to targeted proteins, which are then recognized by the 26S proteasome composed of adenosine triphosphate-dependent, multi-catalytic proteases. Damaged or misfolded proteins, as well as regulatory proteins that control many critical cellular functions, are among the targets of this degradation process. Consequently, aberration of the system leads to dysregulation of cellular homeostasis and development of many diseases. Based on the findings, it is not surprising that abnormalities of the system are also associated with the pathogenesis of kidney diseases. In this review, I discuss (1) the basic mechanism of the UPS, and (2) the association between the pathogenesis of kidney diseases and the UPS. Diverse roles of the UPS are implicated in the development of kidney diseases, and further studies on this system may reveal new strategies for overcoming kidney diseases.

Keywords

Protein degradation Ubiquitin 26S proteasome E3 ligase 

Abbreviations

AKI

Acute kidney injury

ALK-5

Activin-like kinase-5

AMP

Adenosine monophosphate

ATP

Adenosine triphosphate

CBP

CREB-binding protein

CREB

cAMP response element binding protein

CKD

Chronic kidney disease

Cks1

cdc kinase subunit 1

ECM

Extracellular matrix

EMT

Epithelial-mesenchymal transition

ET-1

Endothelin-1

ENaC

Epithelial sodium channel

Evi-1

Ectopic viral integration site-1

FoxO

Forkhead box O

GBM

Glomerular basement membrane

HECT

Homologous to E6-AP C-terminus

HIF-α

Hypoxia-inducible factor-α

IGF-I

Insulin-like growth factor-I

IкB

Inhibitor кB

LDL

Low-density lipoprotein

MAFbx

Muscle atrophy F-box

MSG1

Melanocyte-specific gene 1

MuRF1

Muscle ring finger 1

Nedd4

Neural precursor cell-expressed developmentally downregulated 4

NF-кB

Nuclear factor-кB

p27

p27kip1

PI3K

Phosphatidylinositol 3-kinase

PPAR-γ

Peroxisome proliferator-activated receptor-γ

RING

Really interesting new gene

SARA

Smad anchor for receptor activation

SCF

Skp/Cullin/F-box

Sgk1

Serum- and glucocorticoid-inducible protein kinase 1

Ski

Sloan-Kettering Institute proto-oncogene

Skp2

S-phase kinase-associated protein 2

Smurf1

Smad-ubiquitination regulatory factor 1

SnoN

ski-related novel gene N

TβR-I

TGF-β type I receptor

TβR-II

TGF-β type II receptor

TβR

TGF-β receptors

TGF-β

Transforming growth factor-β

TNF

Tumor necrosis factor

UPS

Ubiquitin–proteasome system

UUO

Unilateral ureteral obstruction

pVHL

von Hippel–Lindau protein

VHL

von Hippel–Lindau disease

References

  1. 1.
    Mitch WE, Goldberg AL. Mechanisms of muscle wasting. The role of the ubiquitin–proteasome pathway. N Engl J Med. 1996;335(25):1897–905.PubMedCrossRefGoogle Scholar
  2. 2.
    Rajan V, Mitch WE. Ubiquitin, proteasomes and proteolytic mechanisms activated by kidney disease. Biochim Biophys Acta. 2008;1782(12):795–9. doi:10.1016/j.bbadis.2008.07.007.PubMedCrossRefGoogle Scholar
  3. 3.
    Glickman MH, Ciechanover A. The ubiquitin–proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev. 2002;82(2):373–428. doi:10.1152/physrev.00027.2001.PubMedGoogle Scholar
  4. 4.
    Knecht E, Aguado C, Carcel J, Esteban I, Esteve JM, Ghislat G, et al. Intracellular protein degradation in mammalian cells: recent developments. Cell Mol Life Sci. 2009;66(15):2427–43. doi:10.1007/s00018-009-0030-6.PubMedCrossRefGoogle Scholar
  5. 5.
    Reinstein E, Ciechanover A. Narrative review: protein degradation and human diseases: the ubiquitin connection. Ann Intern Med. 2006;145(9):676–84.PubMedGoogle Scholar
  6. 6.
    Tanaka K. The proteasome: overview of structure and functions. Proc Jpn Acad Ser B Phys Biol Sci. 2009;85(1):12–36. JST.JSTAGE/pjab/85.12.PubMedCrossRefGoogle Scholar
  7. 7.
    Massague J. TGF-beta signal transduction. Annu Rev Biochem. 1998;67:753–91. doi:10.1146/annurev.biochem.67.1.753.PubMedCrossRefGoogle Scholar
  8. 8.
    Border WA, Ruoslahti E. Transforming growth factor-beta in disease: the dark side of tissue repair. J Clin Invest. 1992;90(1):1–7. doi:10.1172/JCI115821.PubMedCrossRefGoogle Scholar
  9. 9.
    Izzi L, Attisano L. Regulation of the TGFbeta signalling pathway by ubiquitin-mediated degradation. Oncogene. 2004;23(11):2071–8. doi:10.1038/sj.onc.1207412.PubMedCrossRefGoogle Scholar
  10. 10.
    Monteleone G, Kumberova A, Croft NM, McKenzie C, Steer HW, MacDonald TT. Blocking Smad7 restores TGF-beta1 signaling in chronic inflammatory bowel disease. J Clin Invest. 2001;108(4):601–9. doi:10.1172/JCI12821.PubMedGoogle Scholar
  11. 11.
    Dong C, Zhu S, Wang T, Yoon W, Li Z, Alvarez RJ, et al. Deficient Smad7 expression: a putative molecular defect in scleroderma. Proc Natl Acad Sci USA. 2002;99(6):3908–13. doi:10.1073/pnas.062010399.PubMedCrossRefGoogle Scholar
  12. 12.
    Wang B, Hao J, Jones SC, Yee MS, Roth JC, Dixon IM. Decreased Smad 7 expression contributes to cardiac fibrosis in the infarcted rat heart. Am J Physiol Heart Circ Physiol. 2002;282(5):H1685–96. doi:10.1152/ajpheart.00266.2001.PubMedGoogle Scholar
  13. 13.
    Fukasawa H, Yamamoto T, Togawa A, Ohashi N, Fujigaki Y, Oda T, et al. Down-regulation of Smad7 expression by ubiquitin-dependent degradation contributes to renal fibrosis in obstructive nephropathy in mice. Proc Natl Acad Sci USA. 2004;101(23):8687–92. doi:10.1073/pnas.0400035101.PubMedCrossRefGoogle Scholar
  14. 14.
    Tahashi Y, Matsuzaki K, Date M, Yoshida K, Furukawa F, Sugano Y, et al. Differential regulation of TGF-beta signal in hepatic stellate cells between acute and chronic rat liver injury. Hepatology. 2002;35(1):49–61. doi:10.1053/jhep.2002.30083.PubMedCrossRefGoogle Scholar
  15. 15.
    Yang J, Zhang X, Li Y, Liu Y. Downregulation of Smad transcriptional corepressors SnoN and Ski in the fibrotic kidney: an amplification mechanism for TGF-beta1 signaling. J Am Soc Nephrol. 2003;14(12):3167–77.PubMedCrossRefGoogle Scholar
  16. 16.
    Kavsak P, Rasmussen RK, Causing CG, Bonni S, Zhu H, Thomsen GH et al. Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation. Mol Cell. 2000;6(6):1365–75. pii: S1097-2765(00)00134-9.Google Scholar
  17. 17.
    Ebisawa T, Fukuchi M, Murakami G, Chiba T, Tanaka K, Imamura T, et al. Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation. J Biol Chem. 2001;276(16):12477–80. doi:10.1074/jbc.C100008200.PubMedCrossRefGoogle Scholar
  18. 18.
    Bonni S, Wang HR, Causing CG, Kavsak P, Stroschein SL, Luo K, et al. TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation. Nat Cell Biol. 2001;3(6):587–95. doi:10.1038/35078562.PubMedCrossRefGoogle Scholar
  19. 19.
    Zhu H, Kavsak P, Abdollah S, Wrana JL, Thomsen GH. A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic pattern formation. Nature. 1999;400(6745):687–93. doi:10.1038/23293.PubMedCrossRefGoogle Scholar
  20. 20.
    Lin X, Liang M, Feng XH. Smurf2 is a ubiquitin E3 ligase mediating proteasome-dependent degradation of Smad2 in transforming growth factor-beta signaling. J Biol Chem. 2000;275(47):36818–22. doi:10.1074/jbc.C000580200.PubMedCrossRefGoogle Scholar
  21. 21.
    Asano Y, Ihn H, Yamane K, Kubo M, Tamaki K. Impaired Smad7-Smurf-mediated negative regulation of TGF-beta signaling in scleroderma fibroblasts. J Clin Invest. 2004;113(2):253–64. doi:10.1172/JCI16269.PubMedGoogle Scholar
  22. 22.
    Ohashi N, Yamamoto T, Uchida C, Togawa A, Fukasawa H, Fujigaki Y, et al. Transcriptional induction of Smurf2 ubiquitin ligase by TGF-beta. FEBS Lett. 2005;579(12):2557–63. doi:10.1016/j.febslet.2005.03.069.PubMedCrossRefGoogle Scholar
  23. 23.
    Tan R, He W, Lin X, Kiss LP, Liu Y. Smad ubiquitination regulatory factor-2 in the fibrotic kidney: regulation, target specificity, and functional implication. Am J Physiol Renal Physiol. 2008;294(5):F1076–83. doi:10.1152/ajprenal.00323.2007.PubMedCrossRefGoogle Scholar
  24. 24.
    Togawa A, Yamamoto T, Suzuki H, Fukasawa H, Ohashi N, Fujigaki Y, et al. Ubiquitin-dependent degradation of Smad2 is increased in the glomeruli of rats with anti-thymocyte serum nephritis. Am J Pathol. 2003;163(4):1645–52.PubMedCrossRefGoogle Scholar
  25. 25.
    Fukasawa H, Yamamoto T, Togawa A, Ohashi N, Fujigaki Y, Oda T, et al. Ubiquitin-dependent degradation of SnoN and Ski is increased in renal fibrosis induced by obstructive injury. Kidney Int. 2006;69(10):1733–40. doi:10.1038/sj.ki.5000261.PubMedCrossRefGoogle Scholar
  26. 26.
    Koinuma D, Shinozaki M, Komuro A, Goto K, Saitoh M, Hanyu A, et al. Arkadia amplifies TGF-beta superfamily signalling through degradation of Smad7. EMBO J. 2003;22(24):6458–70. doi:10.1093/emboj/cdg632.PubMedCrossRefGoogle Scholar
  27. 27.
    Liu W, Rui H, Wang J, Lin S, He Y, Chen M, et al. Axin is a scaffold protein in TGF-beta signaling that promotes degradation of Smad7 by Arkadia. EMBO J. 2006;25(8):1646–58. doi:10.1038/sj.emboj.7601057.PubMedCrossRefGoogle Scholar
  28. 28.
    Liu FY, Li XZ, Peng YM, Liu H, Liu YH. Arkadia-Smad7-mediated positive regulation of TGF-beta signaling in a rat model of tubulointerstitial fibrosis. Am J Nephrol. 2007;27(2):176–83. doi:10.1159/000100518.PubMedGoogle Scholar
  29. 29.
    Liu FY, Li XZ, Peng YM, Liu H, Liu YH. Arkadia regulates TGF-beta signaling during renal tubular epithelial to mesenchymal cell transition. Kidney Int. 2008;73(5):588–94. doi:10.1038/sj.ki.5002713.PubMedCrossRefGoogle Scholar
  30. 30.
    Cheema B, Abas H, Smith B, O’Sullivan AJ, Chan M, Patwardhan A, et al. Investigation of skeletal muscle quantity and quality in end-stage renal disease. Nephrology (Carlton). 15(4):454–63. doi:10.1111/j.1440-1797.2009.01261.x.
  31. 31.
    Qureshi AR, Alvestrand A, Danielsson A, Divino-Filho JC, Gutierrez A, Lindholm B, et al. Factors predicting malnutrition in hemodialysis patients: a cross-sectional study. Kidney Int. 1998;53(3):773–82. doi:10.1046/j.1523-1755.1998.00812.x.PubMedCrossRefGoogle Scholar
  32. 32.
    Wolfe RR. The underappreciated role of muscle in health and disease. Am J Clin Nutr. 2006;84(3):475–82.PubMedGoogle Scholar
  33. 33.
    Lim VS, Kopple JD. Protein metabolism in patients with chronic renal failure: role of uremia and dialysis. Kidney Int. 2000;58(1):1–10. doi:10.1046/j.1523-1755.2000.00135.x.PubMedCrossRefGoogle Scholar
  34. 34.
    Hasselgren PO, James JH, Benson DW, Hall-Angeras M, Angeras U, Hiyama DT, et al. Total and myofibrillar protein breakdown in different types of rat skeletal muscle: effects of sepsis and regulation by insulin. Metabolism. 1989;38(7):634–40.PubMedCrossRefGoogle Scholar
  35. 35.
    Tiao G, Fagan JM, Samuels N, James JH, Hudson K, Lieberman M, et al. Sepsis stimulates nonlysosomal, energy-dependent proteolysis and increases ubiquitin mRNA levels in rat skeletal muscle. J Clin Invest. 1994;94(6):2255–64. doi:10.1172/JCI117588.PubMedCrossRefGoogle Scholar
  36. 36.
    Fang CH, Tiao G, James H, Ogle C, Fischer JE, Hasselgren PO. Burn injury stimulates multiple proteolytic pathways in skeletal muscle, including the ubiquitin-energy-dependent pathway. J Am Coll Surg. 1995;180(2):161–70.PubMedGoogle Scholar
  37. 37.
    Lawson DH, Richmond A, Nixon DW, Rudman D. Metabolic approaches to cancer cachexia. Annu Rev Nutr. 1982;2:277–301. doi:10.1146/annurev.nu.02.070182.001425.PubMedCrossRefGoogle Scholar
  38. 38.
    Baracos VE, DeVivo C, Hoyle DH, Goldberg AL. Activation of the ATP–ubiquitin–proteasome pathway in skeletal muscle of cachectic rats bearing a hepatoma. Am J Physiol. 1995;268(5 Pt 1):E996–1006.PubMedGoogle Scholar
  39. 39.
    Temparis S, Asensi M, Taillandier D, Aurousseau E, Larbaud D, Obled A, et al. Increased ATP-ubiquitin-dependent proteolysis in skeletal muscles of tumor-bearing rats. Cancer Res. 1994;54(21):5568–73.PubMedGoogle Scholar
  40. 40.
    Wang X, Hu Z, Hu J, Du J, Mitch WE. Insulin resistance accelerates muscle protein degradation: activation of the ubiquitin–proteasome pathway by defects in muscle cell signaling. Endocrinology. 2006;147(9):4160–8. doi:10.1210/en.2006-0251.PubMedCrossRefGoogle Scholar
  41. 41.
    Reaich D, Channon SM, Scrimgeour CM, Daley SE, Wilkinson R, Goodship TH. Correction of acidosis in humans with CRF decreases protein degradation and amino acid oxidation. Am J Physiol. 1993;265(2 Pt 1):E230–5.PubMedGoogle Scholar
  42. 42.
    Graham KA, Reaich D, Channon SM, Downie S, Goodship TH. Correction of acidosis in hemodialysis decreases whole-body protein degradation. J Am Soc Nephrol. 1997;8(4):632–7.PubMedGoogle Scholar
  43. 43.
    Pickering WP, Price SR, Bircher G, Marinovic AC, Mitch WE, Walls J. Nutrition in CAPD: serum bicarbonate and the ubiquitin–proteasome system in muscle. Kidney Int. 2002;61(4):1286–92. doi:10.1046/j.1523-1755.2002.00276.x.PubMedCrossRefGoogle Scholar
  44. 44.
    Mitch WE, Medina R, Grieber S, May RC, England BK, Price SR, et al. Metabolic acidosis stimulates muscle protein degradation by activating the adenosine triphosphate-dependent pathway involving ubiquitin and proteasomes. J Clin Invest. 1994;93(5):2127–33. doi:10.1172/JCI117208.PubMedCrossRefGoogle Scholar
  45. 45.
    Price SR, Bailey JL, Wang X, Jurkovitz C, England BK, Ding X, et al. Muscle wasting in insulinopenic rats results from activation of the ATP-dependent, ubiquitin–proteasome proteolytic pathway by a mechanism including gene transcription. J Clin Invest. 1996;98(8):1703–8. doi:10.1172/JCI118968.PubMedCrossRefGoogle Scholar
  46. 46.
    Stenvinkel P, Heimburger O, Paultre F, Diczfalusy U, Wang T, Berglund L, et al. Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int. 1999;55(5):1899–911. doi:10.1046/j.1523-1755.1999.00422.x.PubMedCrossRefGoogle Scholar
  47. 47.
    Song YH, Li Y, Du J, Mitch WE, Rosenthal N, Delafontaine P. Muscle-specific expression of IGF-1 blocks angiotensin II-induced skeletal muscle wasting. J Clin Invest. 2005;115(2):451–8. doi:10.1172/JCI22324.PubMedGoogle Scholar
  48. 48.
    May RC, Kelly RA, Mitch WE. Metabolic acidosis stimulates protein degradation in rat muscle by a glucocorticoid-dependent mechanism. J Clin Invest. 1986;77(2):614–21. doi:10.1172/JCI112344.PubMedCrossRefGoogle Scholar
  49. 49.
    Hu Z, Wang H, Lee IH, Du J, Mitch WE. Endogenous glucocorticoids and impaired insulin signaling are both required to stimulate muscle wasting under pathophysiological conditions in mice. J Clin Invest. 2009;119(10):3059–69. doi:10.1172/JCI38770.PubMedGoogle Scholar
  50. 50.
    Bailey JL, Zheng B, Hu Z, Price SR, Mitch WE. Chronic kidney disease causes defects in signaling through the insulin receptor substrate/phosphatidylinositol 3-kinase/Akt pathway: implications for muscle atrophy. J Am Soc Nephrol. 2006;17(5):1388–94. doi:10.1681/ASN.2004100842.PubMedCrossRefGoogle Scholar
  51. 51.
    Du J, Wang X, Miereles C, Bailey JL, Debigare R, Zheng B, et al. Activation of caspase-3 is an initial step triggering accelerated muscle proteolysis in catabolic conditions. J Clin Invest. 2004;113(1):115–23. doi:10.1172/JCI18330.PubMedGoogle Scholar
  52. 52.
    Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, et al. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science. 2001;294(5547):1704–8. doi:10.1126/science.1065874.PubMedCrossRefGoogle Scholar
  53. 53.
    Lecker SH, Jagoe RT, Gilbert A, Gomes M, Baracos V, Bailey J, et al. Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression. FASEB J. 2004;18(1):39–51. doi:10.1096/fj.03-0610com.PubMedCrossRefGoogle Scholar
  54. 54.
    Lee SW, Dai G, Hu Z, Wang X, Du J, Mitch WE. Regulation of muscle protein degradation: coordinated control of apoptotic and ubiquitin–proteasome systems by phosphatidylinositol 3 kinase. J Am Soc Nephrol. 2004;15(6):1537–45.PubMedCrossRefGoogle Scholar
  55. 55.
    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(1):9–22.PubMedCrossRefGoogle Scholar
  56. 56.
    Polyak K, Lee MH, Erdjument-Bromage H, Koff A, Roberts JM, Tempst P, et al. Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. Cell. 1994;78(1):59–66. pii: 0092-8674(94)90572-X.Google Scholar
  57. 57.
    Kawamata N, Morosetti R, Miller CW, Park D, Spirin KS, Nakamaki T, et al. Molecular analysis of the cyclin-dependent kinase inhibitor gene p27/Kip1 in human malignancies. Cancer Res. 1995;55(11):2266–9.PubMedGoogle Scholar
  58. 58.
    Morosetti R, Kawamata N, Gombart AF, Miller CW, Hatta Y, Hirama T, et al. Alterations of the p27KIP1 gene in non-Hodgkin’s lymphomas and adult T-cell leukemia/lymphoma. Blood. 1995;86(5):1924–30.PubMedGoogle Scholar
  59. 59.
    Shimada M, Kitagawa K, Dobashi Y, Isobe T, Hattori T, Uchida C, et al. High expression of Pirh2, an E3 ligase for p27, is associated with low expression of p27 and poor prognosis in head and neck cancers. Cancer Sci. 2009;100(5):866–72.PubMedCrossRefGoogle Scholar
  60. 60.
    Esposito V, Baldi A, De Luca A, Groger AM, Loda M, Giordano GG, et al. Prognostic role of the cyclin-dependent kinase inhibitor p27 in non-small cell lung cancer. Cancer Res. 1997;57(16):3381–5.PubMedGoogle Scholar
  61. 61.
    Thomas GV, Szigeti K, Murphy M, Draetta G, Pagano M, Loda M. Down-regulation of p27 is associated with development of colorectal adenocarcinoma metastases. Am J Pathol. 1998;153(3):681–7.PubMedCrossRefGoogle Scholar
  62. 62.
    Ciaparrone M, Yamamoto H, Yao Y, Sgambato A, Cattoretti G, Tomita N, et al. Localization and expression of p27KIP1 in multistage colorectal carcinogenesis. Cancer Res. 1998;58(1):114–22.PubMedGoogle Scholar
  63. 63.
    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(4):193–9.PubMedCrossRefGoogle Scholar
  64. 64.
    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(9):5043–8. doi:10.1073/pnas.081474898.PubMedCrossRefGoogle Scholar
  65. 65.
    Palmqvist R, Stenling R, Oberg A, Landberg G. Prognostic significance of p27(Kip1) expression in colorectal cancer: a clinico-pathological characterization. J Pathol. 1999;188(1):18–23. doi:10.1002/(SICI)1096-9896(199905)188:1<18:AID-PATH311>3.0.CO;2-T.PubMedCrossRefGoogle Scholar
  66. 66.
    Tan P, Cady B, Wanner M, Worland P, Cukor B, Magi-Galluzzi C, et al. The cell cycle inhibitor p27 is an independent prognostic marker in small (T1a, b) invasive breast carcinomas. Cancer Res. 1997;57(7):1259–63.PubMedGoogle Scholar
  67. 67.
    Cote RJ, Shi Y, Groshen S, Feng AC, Cordon-Cardo C, Skinner D, et al. Association of p27Kip1 levels with recurrence and survival in patients with stage C prostate carcinoma. J Natl Cancer Inst. 1998;90(12):916–20.PubMedCrossRefGoogle Scholar
  68. 68.
    Chkhotua AB, Abendroth D, Froeba G, Schelzig H. Up-regulation of cell cycle regulatory genes after renal ischemia/reperfusion: differential expression of p16(INK4a), p21(WAF1/CIP1) and p27(Kip1) cyclin-dependent kinase inhibitor genes depending on reperfusion time. Transpl Int. 2006;19(1):72–7. doi:10.1111/j.1432-2277.2005.00227.x.PubMedCrossRefGoogle Scholar
  69. 69.
    Gerth JH, Kriegsmann J, Trinh TT, Stahl RA, Wendt T, Sommer M, et al. Induction of p27KIP1 after unilateral ureteral obstruction is independent of angiotensin II. Kidney Int. 2002;61(1):68–79. doi:10.1046/j.1523-1755.2002.00111.x.PubMedCrossRefGoogle Scholar
  70. 70.
    Terada Y, Inoshita S, Nakashima O, Yamada T, Kuwahara M, Sasaki S, et al. Lovastatin inhibits mesangial cell proliferation via p27Kip1. J Am Soc Nephrol. 1998;9(12):2235–43.PubMedGoogle Scholar
  71. 71.
    Hiromura K, Pippin JW, Fero ML, Roberts JM, Shankland SJ. Modulation of apoptosis by the cyclin-dependent kinase inhibitor p27(Kip1). J Clin Invest. 1999;103(5):597–604. doi:10.1172/JCI5461.PubMedCrossRefGoogle Scholar
  72. 72.
    Ophascharoensuk V, Fero ML, Hughes J, Roberts JM, Shankland SJ. The cyclin-dependent kinase inhibitor p27Kip1 safeguards against inflammatory injury. Nat Med. 1998;4(5):575–80.PubMedCrossRefGoogle Scholar
  73. 73.
    Suzuki S, Fukasawa H, Kitagawa K, Uchida C, Hattori T, Isobe T, et al. Renal damage in obstructive nephropathy is decreased in Skp2-deficient mice. Am J Pathol. 2007;171(2):473–83. doi:10.2353/ajpath.2007.070279.PubMedCrossRefGoogle Scholar
  74. 74.
    Suzuki S, Fukasawa H, Misaki T, Togawa A, Ohashi N, Kitagawa K, et al. Up-regulation of Cks1 and Skp2 with TNFalpha/NF-kappaB signaling in chronic progressive nephropathy. Genes Cells. 2011;16(11):1110–20. doi:10.1111/j.1365-2443.2011.01553.x.PubMedCrossRefGoogle Scholar
  75. 75.
    Liddle GW, Bledsoe T, Coppage WSJ. A familial renal disorder simulating primary aldosteronism but with negligible aldosterone secretion. Trans Assoc Am Physicians. 1963;76:199–213.Google Scholar
  76. 76.
    Botero-Velez M, Curtis JJ, Warnock DG. Brief report: Liddle’s syndrome revisited—a disorder of sodium reabsorption in the distal tubule. N Engl J Med. 1994;330(3):178–81.PubMedCrossRefGoogle Scholar
  77. 77.
    Staub O, Gautschi I, Ishikawa T, Breitschopf K, Ciechanover A, Schild L, et al. Regulation of stability and function of the epithelial Na+ channel (ENaC) by ubiquitination. EMBO J. 1997;16(21):6325–36. doi:10.1093/emboj/16.21.6325.PubMedCrossRefGoogle Scholar
  78. 78.
    Shimkets RA, Warnock DG, Bositis CM, Nelson-Williams C, Hansson JH, Schambelan M, et al. Liddle’s syndrome: heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel. Cell. 1994;79(3):407–14. pii: 0092-8674(94)90250-X.Google Scholar
  79. 79.
    Henry PC, Kanelis V, O’Brien MC, Kim B, Gautschi I, Forman-Kay J, et al. Affinity and specificity of interactions between Nedd4 isoforms and the epithelial Na+ channel. J Biol Chem. 2003;278(22):20019–28. doi:10.1074/jbc.M211153200.PubMedCrossRefGoogle Scholar
  80. 80.
    Kanelis V, Bruce MC, Skrynnikov NR, Rotin D, Forman-Kay JD. Structural determinants for high-affinity binding in a Nedd4 WW3* domain-Comm PY motif complex. Structure. 2006;14(3):543–53. doi:10.1016/j.str.2005.11.018.PubMedCrossRefGoogle Scholar
  81. 81.
    Loffing-Cueni D, Flores SY, Sauter D, Daidie D, Siegrist N, Meneton P, et al. Dietary sodium intake regulates the ubiquitin-protein ligase nedd4-2 in the renal collecting system. J Am Soc Nephrol. 2006;17(5):1264–74. doi:10.1681/ASN.2005060659.PubMedCrossRefGoogle Scholar
  82. 82.
    Abriel H, Loffing J, Rebhun JF, Pratt JH, Schild L, Horisberger JD, et al. Defective regulation of the epithelial Na+ channel by Nedd4 in Liddle’s syndrome. J Clin Invest. 1999;103(5):667–73. doi:10.1172/JCI5713.PubMedCrossRefGoogle Scholar
  83. 83.
    Kamynina E, Debonneville C, Bens M, Vandewalle A, Staub O. A novel mouse Nedd4 protein suppresses the activity of the epithelial Na+ channel. FASEB J. 2001;15(1):204–14. doi:10.1096/fj.00-0191com.PubMedCrossRefGoogle Scholar
  84. 84.
    Lu C, Pribanic S, Debonneville A, Jiang C, Rotin D. The PY motif of ENaC, mutated in Liddle syndrome, regulates channel internalization, sorting and mobilization from subapical pool. Traffic. 2007;8(9):1246–64. doi:10.1111/j.1600-0854.2007.00602.x.PubMedCrossRefGoogle Scholar
  85. 85.
    Debonneville C, Flores SY, Kamynina E, Plant PJ, Tauxe C, Thomas MA, et al. Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression. EMBO J. 2001;20(24):7052–9. doi:10.1093/emboj/20.24.7052.PubMedCrossRefGoogle Scholar
  86. 86.
    Latif F, Tory K, Gnarra J, Yao M, Duh FM, Orcutt ML, et al. Identification of the von Hippel–Lindau disease tumor suppressor gene. Science. 1993;260(5112):1317–20.PubMedCrossRefGoogle Scholar
  87. 87.
    Rathmell WK, Chen S. VHL inactivation in renal cell carcinoma: implications for diagnosis, prognosis and treatment. Expert Rev Anticancer Ther. 2008;8(1):63–73. doi:10.1586/14737140.8.1.63.PubMedCrossRefGoogle Scholar
  88. 88.
    Cockman ME, Masson N, Mole DR, Jaakkola P, Chang GW, Clifford SC, et al. Hypoxia inducible factor-alpha binding and ubiquitylation by the von Hippel–Lindau tumor suppressor protein. J Biol Chem. 2000;275(33):25733–41. doi:10.1074/jbc.M002740200.PubMedCrossRefGoogle Scholar
  89. 89.
    Wenger RH. Cellular adaptation to hypoxia: O2-sensing protein hydroxylases, hypoxia-inducible transcription factors, and O2-regulated gene expression. FASEB J. 2002;16(10):1151–62. doi:10.1096/fj.01-0944rev.PubMedCrossRefGoogle Scholar
  90. 90.
    Clifford SC, Cockman ME, Smallwood AC, Mole DR, Woodward ER, Maxwell PH, et al. Contrasting effects on HIF-1alpha regulation by disease-causing pVHL mutations correlate with patterns of tumourigenesis in von Hippel–Lindau disease. Hum Mol Genet. 2001;10(10):1029–38.PubMedCrossRefGoogle Scholar
  91. 91.
    Maynard MA, Ohh M. Molecular targets from VHL studies into the oxygen-sensing pathway. Curr Cancer Drug Targets. 2005;5(5):345–56.PubMedCrossRefGoogle Scholar
  92. 92.
    Iguchi M, Kakinuma Y, Kurabayashi A, Sato T, Shuin T, Hong SB, et al. Acute inactivation of the VHL gene contributes to protective effects of ischemic preconditioning in the mouse kidney. Nephron Exp Nephrol. 2008;110(3):e82–90. doi:10.1159/000166994.PubMedCrossRefGoogle Scholar
  93. 93.
    Kapitsinou PP, Haase VH. The VHL tumor suppressor and HIF: insights from genetic studies in mice. Cell Death Differ. 2008;15(4):650–9. doi:10.1038/sj.cdd.4402313.PubMedCrossRefGoogle Scholar
  94. 94.
    Percy MJ, Furlow PW, Lucas GS, Li X, Lappin TR, McMullin MF, et al. A gain-of-function mutation in the HIF2A gene in familial erythrocytosis. N Engl J Med. 2008;358(2):162–8. doi:10.1056/NEJMoa073123.PubMedCrossRefGoogle Scholar
  95. 95.
    Bernhardt WM, Wiesener MS, Weidemann A, Schmitt R, Weichert W, Lechler P, et al. Involvement of hypoxia-inducible transcription factors in polycystic kidney disease. Am J Pathol. 2007;170(3):830–42. doi:10.2353/ajpath.2007.060455.PubMedCrossRefGoogle Scholar
  96. 96.
    Star RA. Treatment of acute renal failure. Kidney Int. 1998;54(6):1817–31. doi:10.1046/j.1523-1755.1998.00210.x.PubMedCrossRefGoogle Scholar
  97. 97.
    Itoh M, Takaoka M, Shibata A, Ohkita M, Matsumura Y. Preventive effect of lactacystin, a selective proteasome inhibitor, on ischemic acute renal failure in rats. J Pharmacol Exp Ther. 2001;298(2):501–7.PubMedGoogle Scholar
  98. 98.
    Takaoka M, Itoh M, Hayashi S, Kuro T, Matsumura Y. Proteasome participates in the pathogenesis of ischemic acute renal failure in rats. Eur J Pharmacol. 1999;384(1):43–6. pii: S0014-2999(99)00664-0.Google Scholar
  99. 99.
    Takaoka M, Itoh M, Kohyama S, Shibata A, Ohkita M, Matsumura Y. Proteasome inhibition attenuates renal endothelin-1 production and the development of ischemic acute renal failure in rats. J Cardiovasc Pharmacol. 2000;36(5 Suppl 1):S225–7.PubMedGoogle Scholar
  100. 100.
    Quehenberger P, Bierhaus A, Fasching P, Muellner C, Klevesath M, Hong M, et al. Endothelin 1 transcription is controlled by nuclear factor-kappaB in AGE-stimulated cultured endothelial cells. Diabetes. 2000;49(9):1561–70.PubMedCrossRefGoogle Scholar
  101. 101.
    Jesenberger V, Jentsch S. Deadly encounter: ubiquitin meets apoptosis. Nat Rev Mol Cell Biol. 2002;3(2):112–21. doi:10.1038/nrm731.PubMedCrossRefGoogle Scholar
  102. 102.
    Huber JM, Tagwerker A, Heininger D, Mayer G, Rosenkranz AR, Eller K. The proteasome inhibitor bortezomib aggravates renal ischemia-reperfusion injury. Am J Physiol Renal Physiol. 2009;297(2):F451–60. doi:10.1152/ajprenal.90576.2008.PubMedCrossRefGoogle Scholar
  103. 103.
    Liu L, Yang C, Herzog C, Seth R, Kaushal GP. Proteasome inhibitors prevent cisplatin-induced mitochondrial release of apoptosis-inducing factor and markedly ameliorate cisplatin nephrotoxicity. Biochem Pharmacol. 79(2):137–46. doi:10.1016/j.bcp.2009.08.015.

Copyright information

© Japanese Society of Nephrology 2012

Authors and Affiliations

  1. 1.Renal Division, Department of Internal MedicineIwata City HospitalIwataJapan

Personalised recommendations