ABSTRACT
The basal activity of JNK is low in normal growing cells and inactivated JNK targets p53 for ubiquitination. To elucidate if the C-terminal part of JNK is responsible for its binding to p53, the low background tet-off inducible NIH3T3 cell line was selected by luciferase reporter gene and a double stable C-JNK Aa (203-424) cell line was established. After withdrawing tetracycline, the C-JNK fragment expression was induced and cell growth was dramatically inhibited 24 h later. However, the expresion of p53 was found to be increased after the induction of C-JNK fragment, evaluated by transfecting p21waf-luciferase reporter genes. Our further studies showed that C-JNK fragment could form complex with p53 both in vivo and in vitro. Induction of C-JNK fragment in vivo can increase p53 stability by inhibiting p53 ubiquitination.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Errede B, Levin BE . A conserved kinase cascade for MAP kinase activation in yeast. Curr Opin Cell Biol 1993; 5: 254–60.
Davis RJ . Signal transduction by the JNK group of MAP kinases. Cell 2000; 103: 239–52.
Marshall CJ . MAP kinase kinase kinase, MAP kinase kinase and MAP kinase. Curr Opin Genet Dev 1994; 4: 82–9.
Kyriakis JM, Avruch J . Sounding the alarm: protein kinases cascades activated by stress and inflammation. J Biol Chem 1996; 271: 24313–6.
Schaeffer HJ, Weber MJ . Mitogen-activated protein kinases: specific messages from ubiquitous messengers. Mol Cell Biol 1999; 19: 2435–44.
Widmann C, Gibson S, Jarpe MB, Johnson GL . Mitogen-activated protein: conservation from yeast to human. Physiol Rev 1999; 79: 143–80.
Jiang Y, Chen C, Li Z, et al. Characterization of the structure and function of a new mitogen-activated protein kinase(p38β). J Biol Chem 1996; 271: 17920–6.
Lopez-Ilasaca M . Signalling from G-protein-coupled receptors to mitogen-activated protein (MAP)-kinase cascades. Biochem Pharmacol 1998; 56: 269–77.
Derijard B, Hibi M, Wu IH, et al. JNK1: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell 1994; 76: 1025–37.
Karin M . The regulation of AP-1 activity by mitogen-activated protein kinases. J Biol Chem 1995; 270: 16483–16486.
Minden A, Karin M . Regulation and function of the JNK subgroup of MAP kinases. Biochem Biophys Acta 1997; 1333: F85–104.
Adler V, Yin Z, Fuchs SY, et al. Regulation of JNK signaling by GSTp. EMBO J 1999; 18: 1321–34.
Fuchs SY, Fried VA, Ronai Z . Stress-activated kinases regulate protein stability. Oncogene 1998; 17: 1483–90.
Fuchs SY, Xie B, Adler V, et al. c-Jun N-terminal kinases target the ubiquitination of their associated transcription factors. J Biol Chem 1997; 272: 32163–8.
Fuchs SY, Adler V, Thomas B, et al. JNK targets p53 ubiquitination and degradation in nonstressed cells. Genes Dev 1998; 12: 2658–63.
Hibi M, Lin A, Smeal T, Minden A, Karin M . Identification of an oncoprotein-and UV-responsive protein kinase that binds and potentiates the c-Jun activation domain. Genes Dev 1993; 7: 2135–48.
Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME . Opposing effects of ERK and JNK-p38 MAPK kinases on apoptosis. Science 1995; 270: 1326–31.
Verheij M, Bose R, Lin XH, et al. Requirement for ceramide-initiated SAPK/JNK signaling in stress induced apoptosis. Nature 1996; 380: 75–9.
Gupta S, Barrett T, Whitmarsh AJ, et al. Selective interation of JNK protein kinase isoforms with transcription factors. EMBO J 1996; 15: 2760–70.
Westwick JK, Bielawska AE, Dbaibo G, et al. Ceramide activates the stress-activated protein kinase. J Biol Chem 1995; 270: 22689–92.
Noguchi K, Kitanaka C, Yamana H, Hannun YA, Brenner DA . Regulation of c-Myc through phosphorylation at Ser-62 and Ser-71 by c-Jun N-terminal kinase. J Biol Chem 1999; 274: 32580–7.
Yamamoto K, Ichijo H, Korsmeyer SJ . BCL-2 is phosphorylated and inactivated by ASK1/Jun N-terminal protein kinase pathway normally activated at G(2)/M. Mol Cell Biol 1999; 19: 8469–78.
Milne DM, Campbell DG, Meek DW, Meek DW . p53 is phosphorylated in vitro and in vivo by an ultraviolet radiation induced protein kinase characteristic of c-Jun kinase JNK1. J Biol Chem 1995; 270: 5511–8.
Tanoue T, adachi M, Moriguchi T, Nishida E . A conserved docking motif in MAP kinases common to substrates, activators and regulators. Nat Cell Biol 2000; 2:270: 110–6.
Thomas B, Yin Z, Anindita B, Ze'ev Ronai . Amino-terminal-derived JNK Fragment Alters Expression and Activity of c-Jun, ATF2, and p53 and Increases H2O2-induced Cell Death. J Biol Chem. 2000; 275: 16590–6.
Fuchs SY, Adler V, Pincus MR, Ronai Z . MEKK1/JNK signaling stabilizes and activates p53. Proc Natl Acad Sci USA 1998; 95: 10541–6.
Acknowledgements
This work was supported by National Natural Science Foundation of China (No.30270556) and The National Basic Research Program (No.2002CB513004). We would also like to thank Dr. Ze'ev Ronai (Department of Oncological Sciences, Mount Sinai School of Medicin. NY, USA) for the constructions of some plasmids and cell lines.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
YIN, Z., SIMA, J., WU, Y. et al. The effect of C-terminal fragment of JNK2 on the stability of p53 and cell proliferation. Cell Res 14, 434–438 (2004). https://doi.org/10.1038/sj.cr.7290244
Received:
Revised:
Accepted:
Issue date:
DOI: https://doi.org/10.1038/sj.cr.7290244
