Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
The c-Jun N-terminal kinase (JNK) signaling pathway is known to mediate both survival and apoptosis of tumor cells. Although JNK1 and JNK2 have been shown to differentially regulate the development of skin cancer, the underlying mechanistic basis remains unclear. Here, we demonstrate that JNK1, but not JNK2, interacts with and phosphorylates Myt1 ex vivo and in vitro. UVA induces substantial apoptosis in JNK wild-type (JNK(+/+)) or JNK2-deficient (JNK2(-/-)) mouse embryonic fibroblasts but has no effect on JNK1-deficient (JNK1(-/-)) cells. In addition, UVA-induced caspase-3cleavage and DNA fragmentation were suppressed by the knockdown of human Myt1 in skin cancer cells. JNK1 deficiency results in suppressed Myt1 phosphorylation and caspase-3cleavage in skin exposed to UVA irradiation. In contrast, the absence of JNK2 induces Myt1 phosphorylation and caspase-3cleavage in skin exposed to UVA. The overexpression of JNK1 with Myt1 promotes cellular apoptosis during the early embryonic development of Xenopus laevis, whereas the presence of JNK2 reduces the phenotype of Myt1-induced apoptotic cell death. Most importantly, JNK1(-/-) mice developed more UVA-induced papillomas than either JNK(+/+) or JNK2(-/-) mice, which was associated with suppressed Myt1 phosphorylation and decreased caspase-3cleavage. Taken together, these data provide mechanistic insights into the distinct roles of the different JNK isoforms, specifically suggesting that the JNK1-mediated phosphorylation of Myt1 plays an important role in UVA-induced apoptosis and the prevention of skin carcinogenesis.
Bachelor,
UVA-mediated activation of signaling pathways involved in skin tumor promotion and progression.
2004, Pubmed
Bachelor,
UVA-mediated activation of signaling pathways involved in skin tumor promotion and progression.
2004,
Pubmed
Bode,
The functional contrariety of JNK.
2007,
Pubmed
Caffrey,
The evolution of the MAP kinase pathways: coduplication of interacting proteins leads to new signaling cascades.
1999,
Pubmed
Carter,
Loss of XChk1 function triggers apoptosis after the midblastula transition in Xenopus laevis embryos.
2003,
Pubmed
,
Xenbase
Chang,
Proteases for cell suicide: functions and regulation of caspases.
2000,
Pubmed
Chen,
Contrasting roles of NF-kappaB and JNK in arsenite-induced p53-independent expression of GADD45alpha.
2001,
Pubmed
Choi,
The tumor suppressor p16(INK4a) prevents cell transformation through inhibition of c-Jun phosphorylation and AP-1 activity.
2005,
Pubmed
Davis,
Signal transduction by the JNK group of MAP kinases.
2000,
Pubmed
Dong,
AP-1/jun is required for early Xenopus development and mediates mesoderm induction by fibroblast growth factor but not by activin.
1996,
Pubmed
,
Xenbase
Evan,
A matter of life and cell death.
1998,
Pubmed
Fattaey,
Myt1: a Wee1-type kinase that phosphorylates Cdc2 on residue Thr14.
1997,
Pubmed
Fernandes-Alnemri,
CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme.
1994,
Pubmed
Fuchs,
MEKK1/JNK signaling stabilizes and activates p53.
1998,
Pubmed
Fuchs,
JNK targets p53 ubiquitination and degradation in nonstressed cells.
1998,
Pubmed
Gu,
Deregulation of Cdc2 kinase induces caspase-3 activation and apoptosis.
2003,
Pubmed
,
Xenbase
Hemmati,
Cooperative effect of p21Cip1/WAF-1 and 14-3-3sigma on cell cycle arrest and apoptosis induction by p14ARF.
2008,
Pubmed
Hensey,
A developmental timer that regulates apoptosis at the onset of gastrulation.
1997,
Pubmed
,
Xenbase
Inoue,
The Polo-like kinase Plx1 interacts with and inhibits Myt1 after fertilization of Xenopus eggs.
2005,
Pubmed
,
Xenbase
Ip,
Signal transduction by the c-Jun N-terminal kinase (JNK)--from inflammation to development.
1998,
Pubmed
Jaeschke,
JNK2 is a positive regulator of the cJun transcription factor.
2006,
Pubmed
Johnson,
Cellular transformation and malignancy induced by ras require c-jun.
1996,
Pubmed
Kelfkens,
Tumorigenesis by short-wave ultraviolet A: papillomas versus squamous cell carcinomas.
1991,
Pubmed
Kennedy,
Suppression of Ras-stimulated transformation by the JNK signal transduction pathway.
2003,
Pubmed
Liu,
Overproduction of human Myt1 kinase induces a G2 cell cycle delay by interfering with the intracellular trafficking of Cdc2-cyclin B1 complexes.
1999,
Pubmed
Lu,
Cell apoptosis: requirement of H2AX in DNA ladder formation, but not for the activation of caspase-3.
2006,
Pubmed
McGowan,
Cell cycle regulation of human WEE1.
1995,
Pubmed
Milne,
p53 is phosphorylated in vitro and in vivo by an ultraviolet radiation-induced protein kinase characteristic of the c-Jun kinase, JNK1.
1995,
Pubmed
Morgan,
Cyclin-dependent kinases: engines, clocks, and microprocessors.
1997,
Pubmed
Mueller,
Cell cycle regulation of a Xenopus Wee1-like kinase.
1995,
Pubmed
,
Xenbase
Mueller,
Myt1: a membrane-associated inhibitory kinase that phosphorylates Cdc2 on both threonine-14 and tyrosine-15.
1995,
Pubmed
,
Xenbase
Norbury,
Regulatory phosphorylation of the p34cdc2 protein kinase in vertebrates.
1991,
Pubmed
,
Xenbase
Okumura,
Akt inhibits Myt1 in the signalling pathway that leads to meiotic G2/M-phase transition.
2002,
Pubmed
Ongkeko,
Inactivation of Cdc2 increases the level of apoptosis induced by DNA damage.
1995,
Pubmed
Palmer,
A link between MAP kinase and p34(cdc2)/cyclin B during oocyte maturation: p90(rsk) phosphorylates and inactivates the p34(cdc2) inhibitory kinase Myt1.
1998,
Pubmed
,
Xenbase
Parker,
Identification of a 95-kDa WEE1-like tyrosine kinase in HeLa cells.
1995,
Pubmed
Peter,
A new role for Mos in Xenopus oocyte maturation: targeting Myt1 independently of MAPK.
2002,
Pubmed
,
Xenbase
Pulverer,
Phosphorylation of c-jun mediated by MAP kinases.
1991,
Pubmed
She,
Deficiency of c-Jun-NH(2)-terminal kinase-1 in mice enhances skin tumor development by 12-O-tetradecanoylphorbol-13-acetate.
2002,
Pubmed
Sible,
Zygotic transcription is required to block a maternal program of apoptosis in Xenopus embryos.
1997,
Pubmed
,
Xenbase
Smeal,
Oncogenic and transcriptional cooperation with Ha-Ras requires phosphorylation of c-Jun on serines 63 and 73.
1991,
Pubmed
Stack,
Developmentally regulated activation of apoptosis early in Xenopus gastrulation results in cyclin A degradation during interphase of the cell cycle.
1997,
Pubmed
,
Xenbase
Sterenborg,
Tumorigenesis by a long wavelength UV-A source.
1990,
Pubmed
Tournier,
Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway.
2000,
Pubmed
Vaux,
Cell death in development.
1999,
Pubmed
Wells,
The C-terminal domain of the Cdc2 inhibitory kinase Myt1 interacts with Cdc2 complexes and is required for inhibition of G(2)/M progression.
1999,
Pubmed
Weston,
The JNK signal transduction pathway.
2002,
Pubmed
Xia,
Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis.
1995,
Pubmed
Xu,
Involvement of Ras/Raf/AP-1 in BMP-4 signaling during Xenopus embryonic development.
1996,
Pubmed
,
Xenbase
Yang,
Differentiation of CD4+ T cells to Th1 cells requires MAP kinase JNK2.
1998,
Pubmed
Yuan,
Caspase activity sows the seeds of neuronal death.
1999,
Pubmed
de Laat,
Carcinogenesis induced by UVA (365-nm) radiation: the dose-time dependence of tumor formation in hairless mice.
1997,
Pubmed
