title: p53 and c-Jun functionally synergize in the regulation of the DNA repair gene hMSH2 in response to UV.
abstract: The tumor suppresser protein p53 is critical for guarding the genome from incorporation of damaged DNA (Lane, D. P. (1992) Nature 358, 15-16). A relevant stress that activates p53 function is UV light (Noda, A., Toma-Aiba, Y., and Fujiwara, Y. (2000) Oncogene 19, 21-31). Another well known component of the mammalian UV response is the transcription factor c-Jun (Angel, P., and Karin, M. (1991) Biochim. Biophys. Acta 1072, 129-157). We show here that upon UV irradiation p53 activates transcription of the human mismatch repair gene MSH2. Interestingly, this up-regulation critically depends on functional interaction with c-Jun. Hence, the synergistic interaction of a proto-oncogene with a tumor suppresser gene is required for the regulation of the mammalian stress response through activation of expression of MSH2.
authors.affiliation: Department of Human Genetics, University of Saarland, Geb. 68, D-66421 Homburg/Saar, Germany.
authors.forename: S J
authors.initials: SJ
authors.lastname: Scherer
authors.forename: S M
authors.initials: SM
authors.lastname: Maier
authors.forename: M
authors.initials: M
authors.lastname: Seifert
authors.forename: R G
authors.initials: RG
authors.lastname: Hanselmann
authors.forename: K D
authors.initials: KD
authors.lastname: Zang
authors.forename: H K
authors.initials: HK
authors.lastname: Muller-Hermelink
authors.forename: P
authors.initials: P
authors.lastname: Angel
authors.forename: C
authors.initials: C
authors.lastname: Welter
authors.forename: M
authors.initials: M
authors.lastname: Schartl
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D004247:DNA; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D051718:MutS Homolog 2 Protein; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D016159:Tumor Suppressor Protein p53; D004247:DNA; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein