jun-NH2-terminal kinase activation mediated by UV-induced DNA lesions in melanoma and fibroblast cells

V. Adler, S. Y. Fuchs, J. Kim, Andrew Kraft, M. P. King, J. Pelling, Z. Ronai

Research output: Contribution to journalArticle

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Abstract

jun-NH2-terminal kinase (JNK) belongs to a family of protein kinases that phosphorylates c-Jun, ATF2, and Elk1 in response to various forms of stress including UV irradiation and heat shock. Although in previous studies we have demonstrated the importance of membrane components for JNK activation by UV irradiation, here we have elucidated the role of DNA damage in this response. We show that in vitro-irradiated or sonicated DNA that is added to proteins prepared from UV-treated cells can further induce JNK activation in a dose- dependent manner. When compared with UV-B (300 nm), UV-C (254 nm), which is better absorbed by the DNA, is significantly more potent in activating JNK. Furthermore, when wavelengths lower than 300 nm were filtered out, UV-B was no longer able to activate JNK. With the aid of melanoma and fibroblast cells, which exhibit different resistances to irradiation and require different UV doses to generate the same number of DNA lesions, we demonstrate that above a threshold level of 0.45 lesions and up to 0.75 lesions per 1875 bp, the degree of JNK activation correlates with the amount of lesions induced by UV-C irradiation. Finally, to explore the role of nuclear and mitochondrial DNA (mtDNA) in mediating JNK activation after UV irradiation, we have used cells that lack mtDNA. Although the lack of mtDNA did not impair the ability of UV to activate JNK, when enucleated, these cells had lost the ability to activate JNK in response to UV irradiation. Overall, our results suggest that DNA damage in the nuclear compartment is an essential component that acts in concert with membrane-anchored proteins to mediate c-Jun phosphorylation by JNK.

Original languageEnglish (US)
Pages (from-to)1437-1446
Number of pages10
JournalCell Growth and Differentiation
Volume6
Issue number11
StatePublished - 1995
Externally publishedYes

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JNK Mitogen-Activated Protein Kinases
Melanoma
Fibroblasts
DNA
Mitochondrial DNA
DNA Damage
Protein Kinases
Shock
Membrane Proteins
Hot Temperature
Phosphorylation
Membranes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Adler, V., Fuchs, S. Y., Kim, J., Kraft, A., King, M. P., Pelling, J., & Ronai, Z. (1995). jun-NH2-terminal kinase activation mediated by UV-induced DNA lesions in melanoma and fibroblast cells. Cell Growth and Differentiation, 6(11), 1437-1446.

jun-NH2-terminal kinase activation mediated by UV-induced DNA lesions in melanoma and fibroblast cells. / Adler, V.; Fuchs, S. Y.; Kim, J.; Kraft, Andrew; King, M. P.; Pelling, J.; Ronai, Z.

In: Cell Growth and Differentiation, Vol. 6, No. 11, 1995, p. 1437-1446.

Research output: Contribution to journalArticle

Adler, V, Fuchs, SY, Kim, J, Kraft, A, King, MP, Pelling, J & Ronai, Z 1995, 'jun-NH2-terminal kinase activation mediated by UV-induced DNA lesions in melanoma and fibroblast cells', Cell Growth and Differentiation, vol. 6, no. 11, pp. 1437-1446.
Adler, V. ; Fuchs, S. Y. ; Kim, J. ; Kraft, Andrew ; King, M. P. ; Pelling, J. ; Ronai, Z. / jun-NH2-terminal kinase activation mediated by UV-induced DNA lesions in melanoma and fibroblast cells. In: Cell Growth and Differentiation. 1995 ; Vol. 6, No. 11. pp. 1437-1446.
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