Neurobiology of Aging
Volume 29, Issue 10 , Pages 1474-1484 , October 2008

Enhanced proteasome-dependent degradation of the CDK inhibitor p27kip1 in immortalized lymphocytes from Alzheimer's dementia patients

  • Úrsula Muñoz

      Affiliations

    • Department of Cellular and Molecular Pathophysiology, Centro de Investigaciones Biológicas (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain
  • ,
  • Fernando Bartolomé

      Affiliations

    • Department of Cellular and Molecular Pathophysiology, Centro de Investigaciones Biológicas (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain
  • ,
  • Félix Bermejo

      Affiliations

    • Hospital Doce de Octubre, Cra de Andalucía s/n, 28041 Madrid, Spain
  • ,
  • Ángeles Martín-Requero

      Affiliations

    • Department of Cellular and Molecular Pathophysiology, Centro de Investigaciones Biológicas (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain
    • Corresponding Author InformationCorresponding author. Tel.: +34 91 837 3112; fax: +34 91 536 0432.

Received 10 October 2006 ,Revised 25 January 2007 ,Accepted 8 March 2007.

References 

  1. Andreu EJ, Lledo E, Poch E, Ivorra C, Albero MP, Martinez-Climent JA, et al. BCR-ABL induces the expression of Skp2 through the PI3K pathway to promote p27Kip1 degradation and proliferation of chronic myelogenous leukemia cells. Cancer Res. 2005;65:3264–3272
  2. Arendt T. Synaptic plasticity and cell cycle activation in neurons are alternative effector pathways: the ‘Dr. Jekyll and Mr. Hyde concept’ of Alzheimer's disease or the yin and yang of neuroplasticity. Prog. Neurobiol. 2003;71:83–248
  3. Blandini F, Sinforiani E, Pacchetti C, Samuele A, Bazzini E, Zangaglia R, et al. Peripheral proteasome and caspase activity in Parkinson disease and Alzheimer disease. Neurology. 2006;66:529–534
  4. Bloom J, Pagano M. Deregulated degradation of the cdk inhibitor p27 and malignant transformation. Semin. Cancer Biol. 2003;13:41–47
  5. Boehm M, Yoshimoto T, Crook MF, Nallamshetty S, True A, Nabel GJ, et al. A growth factor-dependent nuclear kinase phosphorylates p27(Kip1) and regulates cell cycle progression. EMBO J. 2002;21:3390–3401
  6. Bowser R, Smith MA. Cell cycle proteins in Alzheimer's disease: plenty of wheels but no cycle. J. Alzheimers Dis. 2002;4:249–254
  7. Braun-Dullaeus RC, Mann MJ, Ziegler A, von der Leyen HE, Dzaum VJ. A novel role for the cyclin-dependent kinase inhibitor p27(Kip1) in angiotensin II-stimulated vascular smooth muscle cell hypertrophy. J. Clin. Invest. 1999;104:815–823
  8. Copani A, Uberti D, Sortino MA, Bruno V, Nicoletti F, Memo M. Activation of cell-cycle-associated proteins in neuronal death: a mandatory or dispensable path?. Trends Neurosci. 2001;24:25–31
  9. Cuevas N, Urcelay E, Hermida OG, Saíz RA, Bermejo F, Ayuso MS, et al. Ca2+/calmodulin-dependent modulation of cell cycle elements pRb and p27kip1 involved in the enhanced proliferation of lymphoblasts from patients with Alzheimer dementia. Neurobiol. Dis. 2003;13:254–263
  10. Deb TB, Coticchia CM, Dickson RB. Calmodulin-mediated activation of Akt regulates survival of c-Myc-overexpressing mouse mammary carcinoma cells. J. Biol. Chem. 2004;279:38903–38911
  11. de Vrij FM, Fischer DF, van Leeuwen FW, Hol EM. Protein quality control in Alzheimer's disease by the ubiquitin proteasome system. Prog. Neurobiol. 2004;74:249–270
  12. Dick LR, Cruikshank AA, Destree AT, Grenier L, McCormack TA, Melandri FD, et al. Mechanistic studies on the inactivation of the proteasome by lactacystin in cultured cells. J. Biol. Chem. 1997;272:182–188
  13. Dijkers PF, Medema RH, Pals C, Banerji L, Thomas NS, Lam EW, et al. Forkhead transcription factor FKHR-L1 modulates cytokine-dependent transcriptional regulation of p27(KIP1). Mol. Cell. Biol. 2000;20:9138–9148
  14. Fero ML, Rivkin M, Tasch M, Porter P, Carow CE, Firpo E, et al. A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27(Kip1)-deficient mice. Cell. 1996;85:733–744
  15. Fischer R, Julsgart J, Berchtold MW. High affinity calmodulin target sequence in the signalling molecule PI 3-kinase. FEBS Lett. 1998;425:175–177
  16. Griffin RJ, Moloney A, Kelliher M, Johnston JA, Ravid R, Dockery P, et al. Activation of Akt/PKB, increased phosphorylation of Akt substrates and loss and altered distribution of Akt and PTEN are features of Alzheimer's disease pathology. J. Neurochem. 2005;93:105–117
  17. Hengst L, Reed SI. Translational control of p27Kip1 accumulation during the cell cycle. Science. 1996;271:1861–1864
  18. Herrup K, Neve R, Ackerman S, Copani A. Divide and die: cell cycle events as triggers of nerve cell death. J. Neurosci. 2004;24:9232–9239
  19. Ibarreta D, Parrilla R, Ayuso MS. Altered Ca2+ homeostasis in lymphoblasts from patients with late-onset Alzheimer disease. Alzheimer Dis. Assoc. Disord. 1997;11:220–227
  20. Ishida N, Kitagawa M, Hatakeyama S, Nakayama K. Phosphorylation at serine 10, a major phosphorylation site of p27(Kip1), increases its protein stability. J. Biol. Chem. 2000;275:25146–25154
  21. Joyal JL, Burks DJ, Pons S, Matter WF, Vlahos CJ, White MF, et al. Calmodulin activates phosphatidylinositol 3-kinase. J. Biol. Chem. 1997;272:28183–28186
  22. Keller JN, Hanni KB, Markesbery WR. Impaired proteasome function in Alzheimer's disease. J. Neurochem. 2000;75:436–439
  23. Kotake Y, Nakayama K, Ishida N, Nakayama KI. Role of serine 10 phosphorylation in p27 stabilization revealed by analysis of p27 knock-in mice harboring a serine 10 mutation. J. Biol. Chem. 2005;280:1095–1102
  24. Le XF, Pruefer F, Bast RC. HER2-targeting antibodies modulate the cyclin-dependent kinase inhibitor p27Kip1 via multiple signaling pathways. Cell Cycle. 2005;4:87–95
  25. Li DM, Sun H. PTEN/MMAC1/TEP1 suppresses the tumorigenicity and induces G1 cell cycle arrest in human glioblastoma cells. Proc. Natl. Acad. Sci. U.S.A. 1998;95:15406–15411
  26. Liang J, Zubovitz J, Petrocelli T, Kotchetkov R, Connor MK, Han K, et al. PKB/Akt phosphorylates p27, impairs nuclear import of p27 and opposes p27-mediated G1 arrest. Nat. Med. 2002;8:1153–1160
  27. Liu J, Farmer JD, Lane WS, Friedman J, Weissman I, Schreiber SL. Calcineurin is a common target of cyclophilin–cyclosporin A and FKBP–FK506 complexes. Cell. 1991;66:807–815
  28. Marino S, Krimpenfort P, Leung C, van der Korput HA, Trapman J, Camenisch I, et al. PTEN is essential for cell migration but not for fate determination and tumourigenesis in the cerebellum. Development. 2002;129:3513–3522
  29. McShea A, Harris PL, Webster KR, Wahl AF, Smith MA. Abnormal expression of the cell cycle regulators P16 and CDK4 in Alzheimer's disease. Am. J. Pathol. 1997;150:933–939
  30. Millard S, Vidal A, Markus M, Koff A. A U-rich element in the 5′ untranslated region is necessary for the translation of p27 mRNA. Mol. Cell. Biol. 2000;20:5947–5959
  31. Mitsiades N, Mitsiades CS, Poulaki V, Chauhan D, Richardson PG, Hideshima T, et al. Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. Blood. 2002;99:4079–4086
  32. Motti ML, Califano D, Troncone G, De Marco C, Migliaccio I, Palmieri E, et al. Free full text complex regulation of the cyclin-dependent kinase inhibitor p27kip1 in thyroid cancer cells by the PI3K/AKT pathway: regulation of p27kip1 expression and localization. Am. J. Pathol. 2005;166:737–749
  33. Muñoz U, de las Cuevas N, Bartolome F, Hermida OG, Bermejo F, Martin-Requero A. The cyclopentenone 15-deoxy-delta(12,14)-prostaglandin J2 inhibits G1/S transition and retinoblastoma protein phosphorylation in immortalized lymphocytes from Alzheimer's disease patients. Exp. Neurol. 2005;195:508–517
  34. Nagy Z, Combrinck M, Budge M, McShane R. Cell cycle kinesis in lymphocytes in the diagnosis of Alzheimer's disease. Neurosci. Lett. 2002;317:81–84
  35. Nagy Z, Esiri MM, Smith AD. The cell division cycle and the pathophysiology of Alzheimer's disease. Neuroscience. 1998;87:731–739
  36. 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 p27(Kip1), polyploidy and centrosome overduplication. EMBO J. 2000;19:2069–2081
  37. Pagano M, Tam SW, Theodoras AM, Beer-Romero P, DelSal 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
  38. Perez-Garcia MJ, Cena V, de Pablo Y, Llovera M, Comella JX, Soler RM. Glial cell line-derived neurotrophic factor increases intracellular calcium concentration. Role of calcium/calmodulin in the activation of the phosphatidylinositol 3-kinase pathway. J. Biol. Chem. 2004;279:6132–6142
  39. Raina AK, Zhu X, Rottkamp CA, Monteiro M, Takeda A, Smith MA. Cyclin’ toward dementia: cell cycle abnormalities and abortive oncogenesis in Alzheimer disease. J. Neurosci. Res. 2000;61:128–133
  40. Rickle A, Bogdanovic N, Volkman I, Winblad B, Ravid R, Cowburn RF. Akt activity in Alzheimer's disease and other neurodegenerative disorders. Neuroreport. 2004;15:955–959
  41. Sheaff RJ, Groudine M, Gordon M, Roberts JM, Clurman BE. Cyclin E-CDK2 is a regulator of p27Kip1. Genes Dev. 1997;11:1464–1478
  42. Sherr CJ, Roberts JM. Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev. 1995;9:1149–1163
  43. Shin I, Yakes FM, Rojo F, Shin NY, Bakin AV, Baselga J, et al. PKB/Akt mediates cell-cycle progression by phosphorylation of p27(Kip1) at threonine 157 and modulation of its cellular localization. Nat. Med. 2002;8:1145–1152
  44. Slingerland J, Pagano M. Regulation of the cdk inhibitor p27 and its deregulation in cancer. J. Cell. Physiol. 2000;183:10–17
  45. Stein TD, Johnson JA. Lack of neurodegeneration in transgenic mice overexpressing mutant amyloid precursor protein is associated with increased levels of transthyretin and the activation of cell survival pathways. J. Neurosci. 2002;22:7380–7388
  46. Stieler JT, Lederer C, Bruckner MK, Wolf H, Holzer M, Gertz HJ, et al. Impairment of mitogenic activation of peripheral blood lymphocytes in Alzheimer's disease. Neuroreport. 2001;12:3969–3972
  47. Stokoe D, Stephens LR, Copeland T, Gaffney PR, Reese CB, Painter GF, et al. Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B. Science. 1997;277:567–570
  48. Tatebayashi Y, Takeda M, Kashiwagi Y, Okaochi M, Kurumadani T, Sekiyama A, et al. Cell-cycle-dependent abnormal calcium response in fibroblasts from patients with familial Alzheimer's disease. Dementia. 1995;6:9–16
  49. Tokumitsu H, Chijiwa T, Hagiwara M, Mizutani A, Terasawa M, Hidaka H. KN-62, 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-l-tyrosyl]-4-phenylpiperazine, a specific inhibitor of Ca2+/calmodulin-dependent protein kinase II. J. Biol. Chem. 1990;265:4315–4320
  50. Tomoda K, Kubota Y, Kato J. Degradation of the cyclin-dependent-kinase inhibitor p27Kip1 is instigated by Jab1. Nature. 1999;398:160–185
  51. Tsvetkov LM, Yeh KH, Lee SJ, Sun H, Zhang H. p27(Kip1) ubiquitination and degradation is regulated by the SCF(Skp2) complex through phosphorylated Thr187 in p27. Curr. Biol. 1999;9:661–664
  52. Urcelay E, Ibarreta D, Parrilla R, Ayuso MS, Martín-Requero A. Enhanced proliferation of lymphoblasts from patients with Alzheimer dementia associated with calmodulin-dependent activation of the Na+/H+ exchanger. Neurobiol. Dis. 2001;8:289–298
  53. Viglietto G, Motti ML, Bruni P, Melillo RM, D’Alessio A, Califano D, et al. Cytoplasmic relocalization and inhibition of the cyclin-dependent kinase inhibitor p27(Kip1) by PKB/Akt-mediated phosphorylation in breast cancer. Nat. Med. 2002;8:1136–1144
  54. Webber KM, Raina AK, Marlatt MW, Zhu X, Morelli L, Casadesus G, et al. The cell cycle in Alzheimer disease: a unique target for neuropharmacology. Mech. Ageing Dev. 2005;126:1019–1025
  55. Zhu X, Raina AK, Perry G, Smith MA. Alzheimer's disease: the two-hit hypothesis. Lancet Neurol. 2004;3:219–226

PII: S0197-4580(07)00123-6

doi: 10.1016/j.neurobiolaging.2007.03.013

Neurobiology of Aging
Volume 29, Issue 10 , Pages 1474-1484 , October 2008