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Presenilin 1 suppresses the function of c-Jun homodimers via interaction with QM/Jif-1.

Imafuku I, Masaki T, Waragai M, Takeuchi S, Kawabata M, Hirai S, Ohno S, Nee LE, Lippa CF, Kanazawa I, Imagawa M, Okazawa H - J. Cell Biol. (1999)

Bottom Line: By monitoring fluorescent recombinant protein and by gel mobility shift assays, PS1 was shown to accelerate the translocation of QM from the cytoplasm to the nucleus and to thereby suppress the binding of c-Jun homodimer to 12-O-tetradecanoylphorbol-13- acetate (TPA)-responsive element (TRE).PS1 suppressed c-jun-associated apoptosis by retinoic acid in F9 embryonic carcinoma cells, whereas this suppression of apoptosis is attenuated by mutation in PS1.Collectively, the novel function of PS1 via QM/Jif-1 influences c-jun-mediated transcription and apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.

ABSTRACT
Presenilin 1 (PS1) is the causative gene for an autosomal dominant familial Alzheimer's disease (AD) mapped to chromosome 14. Here we show that QM/Jun-interacting factor (Jif)-1, a negative regulator of c-Jun, is a candidate to mediate the function of PS1 in the cell. We screened for proteins that bind to PS1 from a human embryonic brain cDNA library using the two-hybrid method and isolated one clone encoding the QM/Jif-1 gene. The binding of QM/Jif-1 to full-length PS1 was confirmed in vitro by pull-down assay, and in vivo by immunoprecipitation assays with human samples, including AD brains. Immunoelectronmicroscopic analysis showed that QM/Jif-1 and PS1 are colocalized at the endoplasmic reticulum, and the nuclear matrix in human brain neurons. Chloramphenicol acetyltransferase assays in F9 cells showed that PS1 suppresses transactivation by c-Jun/c-Jun but not by c-Jun/c-Fos heterodimers, consistent with the reported function of QM/Jif-1. By monitoring fluorescent recombinant protein and by gel mobility shift assays, PS1 was shown to accelerate the translocation of QM from the cytoplasm to the nucleus and to thereby suppress the binding of c-Jun homodimer to 12-O-tetradecanoylphorbol-13- acetate (TPA)-responsive element (TRE). PS1 suppressed c-jun-associated apoptosis by retinoic acid in F9 embryonic carcinoma cells, whereas this suppression of apoptosis is attenuated by mutation in PS1. Collectively, the novel function of PS1 via QM/Jif-1 influences c-jun-mediated transcription and apoptosis.

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Mentions: Second, we tested whether PS1 affects transcriptional regulation by the other c-jun family members forming an AP-1 complex. Expression of junB and junD enhanced transcription from collagenase 1× TRE CAT reporter plasmid (Fig. 5 d). Transactivation by junD was clearly suppressed by expression of normal and mutant PS1, whereas transactivation by junB was not affected (Fig. 5 d). In this case, suppression of junD-mediated transactivation by normal PS1 was not remarkably different from that by mutant PS1 (Fig. 5 d), in contrast to our observations with c-jun–mediated transactivation (Fig. 5b and Fig. c). In the CAT assays described above, we confirmed that expression of the c-Jun protein was not influenced by cotransfecting PS1, and that expression of normal and mutant PS1 proteins was equivalent (Fig. 5 e). We summarized results from all the CAT assays described above with a histogram showing mean fold transactivations (Fig. 5 f).


Presenilin 1 suppresses the function of c-Jun homodimers via interaction with QM/Jif-1.

Imafuku I, Masaki T, Waragai M, Takeuchi S, Kawabata M, Hirai S, Ohno S, Nee LE, Lippa CF, Kanazawa I, Imagawa M, Okazawa H - J. Cell Biol. (1999)

© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2164975&req=5

Mentions: Second, we tested whether PS1 affects transcriptional regulation by the other c-jun family members forming an AP-1 complex. Expression of junB and junD enhanced transcription from collagenase 1× TRE CAT reporter plasmid (Fig. 5 d). Transactivation by junD was clearly suppressed by expression of normal and mutant PS1, whereas transactivation by junB was not affected (Fig. 5 d). In this case, suppression of junD-mediated transactivation by normal PS1 was not remarkably different from that by mutant PS1 (Fig. 5 d), in contrast to our observations with c-jun–mediated transactivation (Fig. 5b and Fig. c). In the CAT assays described above, we confirmed that expression of the c-Jun protein was not influenced by cotransfecting PS1, and that expression of normal and mutant PS1 proteins was equivalent (Fig. 5 e). We summarized results from all the CAT assays described above with a histogram showing mean fold transactivations (Fig. 5 f).

Bottom Line: By monitoring fluorescent recombinant protein and by gel mobility shift assays, PS1 was shown to accelerate the translocation of QM from the cytoplasm to the nucleus and to thereby suppress the binding of c-Jun homodimer to 12-O-tetradecanoylphorbol-13- acetate (TPA)-responsive element (TRE).PS1 suppressed c-jun-associated apoptosis by retinoic acid in F9 embryonic carcinoma cells, whereas this suppression of apoptosis is attenuated by mutation in PS1.Collectively, the novel function of PS1 via QM/Jif-1 influences c-jun-mediated transcription and apoptosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.

ABSTRACT
Presenilin 1 (PS1) is the causative gene for an autosomal dominant familial Alzheimer's disease (AD) mapped to chromosome 14. Here we show that QM/Jun-interacting factor (Jif)-1, a negative regulator of c-Jun, is a candidate to mediate the function of PS1 in the cell. We screened for proteins that bind to PS1 from a human embryonic brain cDNA library using the two-hybrid method and isolated one clone encoding the QM/Jif-1 gene. The binding of QM/Jif-1 to full-length PS1 was confirmed in vitro by pull-down assay, and in vivo by immunoprecipitation assays with human samples, including AD brains. Immunoelectronmicroscopic analysis showed that QM/Jif-1 and PS1 are colocalized at the endoplasmic reticulum, and the nuclear matrix in human brain neurons. Chloramphenicol acetyltransferase assays in F9 cells showed that PS1 suppresses transactivation by c-Jun/c-Jun but not by c-Jun/c-Fos heterodimers, consistent with the reported function of QM/Jif-1. By monitoring fluorescent recombinant protein and by gel mobility shift assays, PS1 was shown to accelerate the translocation of QM from the cytoplasm to the nucleus and to thereby suppress the binding of c-Jun homodimer to 12-O-tetradecanoylphorbol-13- acetate (TPA)-responsive element (TRE). PS1 suppressed c-jun-associated apoptosis by retinoic acid in F9 embryonic carcinoma cells, whereas this suppression of apoptosis is attenuated by mutation in PS1. Collectively, the novel function of PS1 via QM/Jif-1 influences c-jun-mediated transcription and apoptosis.

Show MeSH
Related in: MedlinePlus