Skip to main content

Advertisement

SpringerLink
Log in

Dynamic Changes of Jab1 and p27kip1 Expression in Injured Rat Sciatic Nerve

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Jun activation domain-binding protein (Jab1) is a multifunctional protein that participates in affecting signaling pathway, controlling cell proliferation and apoptosis, and regulating genomic instability and DNA repair, and acts as a key subunit of COP9 signalosome. p27kip1, a member of the Cip/Kip family of cyclin-dependent kinase inhibitors, was shown to inhibit the enzymatic activity of cyclin–CDK complexes, resulting in cell-cycle arrest at G1. Recent studies have shown that Jab1 directly binds to p27kip1 and induces nuclear export and subsequent degradation in a variety of human cancers, while the association and function of Jab1 and p27kip1 in nervous system lesion and regeneration remain unclear. Here, we performed a sciatic nerve injury model in adult rats and studied the dynamic changes of Jab1 and p27kip1 expression by Western blot. Sciatic nerve crush (SNC) resulted in a significant upregulation of Jab1 and a downregulation of p27kip1. Besides, we observed that Jab1 was expressed widely in Schwann cells (SCs) and had few co-localization in axons by double immunofluorescence staining. In addition, the peak expression of Jab1 was parallel with proliferating cell nuclear antigen (PCNA), and numerous SCs expressing Jab1 were PCNA-positive. Results obtained by co-immunoprecipitation and double labeling further showed their interaction in the sciatic nerve. Thus, these results suggested that Jab1 and p27kip1 may be involved in the pathophysiology of sciatic nerve after SNC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

SNC:

Sciatic nerve crush

SCs:

Schwann cells

PNS:

Peripheral nervous system

CNS:

Central nervous system

PAGE:

Polyacrylamide gel electrophoresis

ECL:

Enhanced chemiluminescence system

BSA:

Bovine serum albumin

PCNA:

Proliferating cell nuclear antigen

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

References

  • Berg JP, Zhou Q, Breuhahn K, Schirmacher P, Patil MA, Chen X, Schafer N, Holler TT, Fischer HP, Buttner R, Gutgemann I (2007) Inverse expression of Jun activation domain binding protein 1 and cell cycle inhibitor p27Kip1: influence on proliferation in hepatocellular carcinoma. Hum Pathol 38(11):1621–1627

    Article  PubMed  CAS  Google Scholar 

  • Bianchi E, Denti S, Granata A, Bossi G, Geginat J, Villa A, Rogge L, Pardi R (2000) Integrin LFA-1 interacts with the transcriptional co-activator JAB1 to modulate AP-1 activity. Nature 404(6778):617–621

    Article  PubMed  CAS  Google Scholar 

  • Burger-Kentischer A, Goebel H, Seiler R, Fraedrich G, Schaefer HE, Dimmeler S, Kleemann R, Bernhagen J, Ihling C (2002) Expression of macrophage migration inhibitory factor in different stages of human atherosclerosis. Circulation 105(13):1561–1566

    Article  PubMed  CAS  Google Scholar 

  • Cao Y, Wang Q, Zhou Z, Wang Y, Liu Y, Ji Y, Liu F (2012) Changes of peroxisome proliferator-activated receptor-gamma on crushed rat sciatic nerves and differentiated primary Schwann cells. J Mol Neurosci 47(2):380–388

    Article  PubMed  CAS  Google Scholar 

  • Carruthers S, Mason J, Papalopulu N (2003) Depletion of the cell-cycle inhibitor p27(Xic1) impairs neuronal differentiation and increases the number of ElrC(+) progenitor cells in Xenopus tropicalis. Mech Dev 120(5):607–616

    Article  PubMed  CAS  Google Scholar 

  • Chamovitz DA, Segal D (2001) JAB1/CSN5 and the COP9 signalosome. A complex situation. EMBO Rep 2(2):96–101

    Article  PubMed  CAS  Google Scholar 

  • Chen Q, Xie W, Kuhn DJ, Voorhees PM, Lopez-Girona A, Mendy D, Corral LG, Krenitsky VP, Xu W, Moutouh-de Parseval L, Webb DR, Mercurio F, Nakayama KI, Nakayama K, Orlowski RZ (2008) Targeting the p27 E3 ligase SCF(Skp2) results in p27- and Skp2-mediated cell-cycle arrest and activation of autophagy. Blood 111(9):4690–4699

    Article  PubMed  CAS  Google Scholar 

  • Claret FX, Hibi M, Dhut S, Toda T, Karin M (1996) A new group of conserved coactivators that increase the specificity of AP-1 transcription factors. Nature 383(6599):453–457

    Article  PubMed  CAS  Google Scholar 

  • Collet JF, Messens J (2010) Structure, function, and mechanism of thioredoxin proteins. Antioxid Redox Signal 13(8):1205–1216

    Article  PubMed  CAS  Google Scholar 

  • Durand B, Gao FB, Raff M (1997) Accumulation of the cyclin-dependent kinase inhibitor p27/Kip1 and the timing of oligodendrocyte differentiation. EMBO J 16(2):306–317

    Article  PubMed  CAS  Google Scholar 

  • Farah MH, Pan BH, Hoffman PN, Ferraris D, Tsukamoto T, Nguyen T, Wong PC, Price DL, Slusher BS, Griffin JW (2011) Reduced BACE1 activity enhances clearance of myelin debris and regeneration of axons in the injured peripheral nervous system. J Neurosci 31(15):5744–5754

    Article  PubMed  CAS  Google Scholar 

  • Fricker FR, Bennett DL (2011) The role of neuregulin-1 in the response to nerve injury. Future Neurol 6(6):809–822

    Article  PubMed  CAS  Google Scholar 

  • Fu SY, Gordon T (1997) The cellular and molecular basis of peripheral nerve regeneration. Mol Neurobiol 14(1–2):67–116

    Article  PubMed  CAS  Google Scholar 

  • Grinspan JB, Marchionni MA, Reeves M, Coulaloglou M, Scherer SS (1996) Axonal interactions regulate Schwann cell apoptosis in developing peripheral nerve: neuregulin receptors and the role of neuregulins. J Neurosci 16(19):6107–6118

    PubMed  CAS  Google Scholar 

  • Hokfelt T, Zhang X, Wiesenfeld-Hallin Z (1994) Messenger plasticity in primary sensory neurons following axotomy and its functional implications. Trends Neurosci 17(1):22–30

    Article  PubMed  CAS  Google Scholar 

  • Hwang CY, Ryu YS, Chung MS, Kim KD, Park SS, Chae SK, Chae HZ, Kwon KS (2004) Thioredoxin modulates activator protein 1 (AP-1) activity and p27Kip1 degradation through direct interaction with Jab1. Oncogene 23(55):8868–8875

    Article  PubMed  CAS  Google Scholar 

  • Ishida N, Hara T, Kamura T, Yoshida M, Nakayama K, Nakayama KI (2002) Phosphorylation of p27Kip1 on serine 10 is required for its binding to CRM1 and nuclear export. J Biol Chem 277(17):14355–14358

    Article  PubMed  CAS  Google Scholar 

  • Jessen KR, Mirsky R (1999) Schwann cells and their precursors emerge as major regulators of nerve development. Trends Neurosci 22(9):402–410

    Article  PubMed  CAS  Google Scholar 

  • Kleemann R, Hausser A, Geiger G, Mischke R, Burger-Kentischer A, Flieger O, Johannes FJ, Roger T, Calandra T, Kapurniotu A, Grell M, Finkelmeier D, Brunner H, Bernhagen J (2000) Intracellular action of the cytokine MIF to modulate AP-1 activity and the cell cycle through Jab1. Nature 408(6809):211–216

    Article  PubMed  CAS  Google Scholar 

  • Konigsmark BW (1970) Methods for the counting of neurons. In: Nauta WJH, Ebbesson SOE (eds) Contemporary research methods in neuroanatomy. Springer, New York, pp 315–340

    Chapter  Google Scholar 

  • Kouvaraki MA, Rassidakis GZ, Tian L, Kumar R, Kittas C, Claret FX (2003) Jun activation domain-binding protein 1 expression in breast cancer inversely correlates with the cell cycle inhibitor p27(Kip1). Cancer Res 63(11):2977–2981

    PubMed  CAS  Google Scholar 

  • Kury P, Stoll G, Muller HW (2001) Molecular mechanisms of cellular interactions in peripheral nerve regeneration. Curr Opin Neurol 14(5):635–639

    Article  PubMed  CAS  Google Scholar 

  • Kwok SF, Solano R, Tsuge T, Chamovitz DA, Ecker JR, Matsui M, Deng XW (1998) Arabidopsis homologs of a c-Jun coactivator are present both in monomeric form and in the COP9 complex, and their abundance is differentially affected by the pleiotropic cop/det/fus mutations. Plant Cell 10(11):1779–1790

    PubMed  CAS  Google Scholar 

  • Li S, Liu X, Ascoli M (2000) p38JAB1 binds to the intracellular precursor of the lutropin/choriogonadotropin receptor and promotes its degradation. J Biol Chem 275(18):13386–13393

    Article  PubMed  CAS  Google Scholar 

  • Lou D, Sun B, Wei H, Deng X, Chen H, Xu D, Li G, Xu H, Wang Y (2012) Spatiotemporal expression of testicular protein kinase 1 after rat sciatic nerve injury. J Mol Neurosci 47(1):180–191

    Article  PubMed  CAS  Google Scholar 

  • Miyazawa K, Himi T, Garcia V, Yamagishi H, Sato S, Ishizaki Y (2000) A role for p27/Kip1 in the control of cerebellar granule cell precursor proliferation. J Neurosci 20(15):5756–5763

    PubMed  CAS  Google Scholar 

  • Morgan DO (1995) Principles of CDK regulation. Nature 374(6518):131–134

    Article  PubMed  CAS  Google Scholar 

  • Nguyen MT, Beck J, Lue H, Funfzig H, Kleemann R, Koolwijk P, Kapurniotu A, Bernhagen J (2003) A 16-residue peptide fragment of macrophage migration inhibitory factor, MIF-(50-65), exhibits redox activity and has MIF-like biological functions. J Biol Chem 278(36):33654–33671

    Article  PubMed  CAS  Google Scholar 

  • Nourse J, Firpo E, Flanagan WM, Coats S, Polyak K, Lee MH, Massague J, Crabtree GR, Roberts JM (1994) Interleukin-2-mediated elimination of the p27Kip1 cyclin-dependent kinase inhibitor prevented by rapamycin. Nature 372(6506):570–573

    Article  PubMed  CAS  Google Scholar 

  • Oono K, Yoneda T, Manabe T, Yamagishi S, Matsuda S, Hitomi J, Miyata S, Mizuno T, Imaizumi K, Katayama T, Tohyama M (2004) JAB1 participates in unfolded protein responses by association and dissociation with IRE1. Neurochem Int 45(5):765–772

    Article  PubMed  CAS  Google Scholar 

  • Osoegawa A, Yoshino I, Kometani T, Yamaguchi M, Kameyama T, Yohena T, Maehara Y (2006) Overexpression of Jun activation domain-binding protein 1 in nonsmall cell lung cancer and its significance in p27 expression and clinical features. Cancer 107(1):154–161

    Article  PubMed  CAS  Google Scholar 

  • Pagano M, Tam SW, Theodoras AM, Beer-Romero P, Del Sal G, Chau V, Yew PR, Draetta GF, Rolfe M (1995) Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27. Science 269(5224):682–685

    Article  PubMed  CAS  Google Scholar 

  • Polyak K, Lee MH, Erdjument-Bromage H, Koff A, Roberts JM, Tempst P, Massague J (1994) Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. Cell 78(1):59–66

    Article  PubMed  CAS  Google Scholar 

  • Rassidakis GZ, Claret FX, Lai R, Zhang Q, Sarris AH, McDonnell TJ, Medeiros LJ (2003) Expression of p27(Kip1) and c-Jun activation binding protein 1 are inversely correlated in systemic anaplastic large cell lymphoma. Clin Cancer Res 9(3):1121–1128

    PubMed  CAS  Google Scholar 

  • Reynisdottir I, Polyak K, Iavarone A, Massague J (1995) Kip/Cip and Ink4 Cdk inhibitors cooperate to induce cell cycle arrest in response to TGF-beta. Genes Dev 9(15):1831–1845

    Article  PubMed  CAS  Google Scholar 

  • Salzer JL, Bunge RP (1980) Studies of Schwann cell proliferation. I. An analysis in tissue culture of proliferation during development, Wallerian degeneration, and direct injury. J Cell Biol 84(3):739–752

    Article  PubMed  CAS  Google Scholar 

  • Sbai O, Devi TS, Melone MA, Feron F, Khrestchatisky M, Singh LP, Perrone L (2010) RAGE-TXNIP axis is required for S100B-promoted Schwann cell migration, fibronectin expression and cytokine secretion. J Cell Sci 123(Pt 24):4332–4339

    Article  PubMed  CAS  Google Scholar 

  • Schwechheimer C, Deng XW (2001) COP9 signalosome revisited: a novel mediator of protein degradation. Trends Cell Biol 11(10):420–426

    Article  PubMed  CAS  Google Scholar 

  • Sengupta R, Holmgren A (2012) The role of thioredoxin in the regulation of cellular processes by S-nitrosylation. Biochim Biophys Acta 1820(6):689–700

    Article  PubMed  CAS  Google Scholar 

  • Sherr CJ, Roberts JM (1999) CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 13(12):1501–1512

    Article  PubMed  CAS  Google Scholar 

  • Shintani S, Li C, Mihara M, Hino S, Nakashiro K, Hamakawa H (2003) Skp2 and Jab1 expression are associated with inverse expression of p27(KIP1) and poor prognosis in oral squamous cell carcinomas. Oncology 65(4):355–362

    Article  PubMed  CAS  Google Scholar 

  • Stemme S, Hansson HA, Holmgren A, Rozell B (1985) Axoplasmic transport of thioredoxin and thioredoxin reductase in rat sciatic nerve. Brain Res 359(1–2):140–146

    Article  PubMed  CAS  Google Scholar 

  • Sui L, Dong Y, Ohno M, Watanabe Y, Sugimoto K, Tai Y, Tokuda M (2001) Jab1 expression is associated with inverse expression of p27(kip1) and poor prognosis in epithelial ovarian tumors. Clin Cancer Res 7(12):4130–4135

    PubMed  CAS  Google Scholar 

  • Tomoda K, Kubota Y, Kato J (1999) Degradation of the cyclin-dependent-kinase inhibitor p27Kip1 is instigated by Jab1. Nature 398(6723):160–165

    Article  PubMed  CAS  Google Scholar 

  • Tomoda K, Kubota Y, Arata Y, Mori S, Maeda M, Tanaka T, Yoshida M, Yoneda-Kato N, Kato JY (2002) The cytoplasmic shuttling and subsequent degradation of p27Kip1 mediated by Jab1/CSN5 and the COP9 signalosome complex. J Biol Chem 277(3):2302–2310

    Article  PubMed  CAS  Google Scholar 

  • Toyoshima H, Hunter T (1994) p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21. Cell 78(1):67–74

    Article  PubMed  CAS  Google Scholar 

  • Wei N, Deng XW (2003) The COP9 signalosome. Annu Rev Cell Dev Biol 19:261–286

    Article  PubMed  CAS  Google Scholar 

  • Yoshioka J, Schreiter ER, Lee RT (2006) Role of thioredoxin in cell growth through interactions with signaling molecules. Antioxid Redox Signal 8(11–12):2143–2151

    Article  PubMed  CAS  Google Scholar 

  • Zezula J, Casaccia-Bonnefil P, Ezhevsky SA, Osterhout DJ, Levine JM, Dowdy SF, Chao MV, Koff A (2001) p21cip1 is required for the differentiation of oligodendrocytes independently of cell cycle withdrawal. EMBO Rep 2(1):27–34

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (grant nos.: 81171140, 21077061, and 31071288) and the Natural Science Foundation of Jiangsu Province (grant no.: BK2009161); this is a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Author information

Authors and Affiliations

  1. Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong, 226001, People’s Republic of China

    Xinghai Cheng, Zhengming Zhou, Guangfei Xu, Jing Zhao, Hao Wu, Long Long, Hai Wen & Youhua Wang

  2. The Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University, Nantong, 226001, People’s Republic of China

    Xingxing Gu

Authors
  1. Xinghai Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhengming Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Guangfei Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jing Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hao Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Long Long
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hai Wen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xingxing Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Youhua Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Youhua Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cheng, X., Zhou, Z., Xu, G. et al. Dynamic Changes of Jab1 and p27kip1 Expression in Injured Rat Sciatic Nerve. J Mol Neurosci 51, 148–158 (2013). https://doi.org/10.1007/s12031-013-9969-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-013-9969-8

Keywords

Search

Navigation