AP-1 mediated retinal photoreceptor apoptosis is independent of N-terminal phosphorylation of c-Jun

Grimm, Christian; Wenzel, Andreas; Behrens, Axel; Hafezi, Farhad; Wagner, Erwin F.; Remé, Charlotte E.

doi:10.1038/sj.cdd.4400871

Cited by 37 publications

(27 citation statements)

References 43 publications

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“…Histologically, in agreement with a previous report (Grimm et al, 2001), retinas of JunAA mice were indistinguishable from CT retinas (Fig. 2, and data not shown).…”

Section: The Junaa Mutation Slows Down Segment Flattening By Polyq-atsupporting

confidence: 81%

“…Interestingly, repression of AP-1 dependent target genes has been proposed to account for light-induced apoptosis of photoreceptors (Grimm et al, 2001;Wenzel et al, 2002). Indeed, despite its lack of transactivation domains, Fra-1 can substitute for c-Fos in light-induced photoreceptor apoptosis, suggesting that AP-1, which usually activates genes, acts as a suppressor of anti-apoptotic or survival photoreceptor genes (Wenzel et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

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Preventing polyglutamine-induced activation of c-Jun delays neuronal dysfunction in a mouse model of SCA7 retinopathy

Mérienne¹,

Friedman²,

Akimoto³

et al. 2007

Neurobiology of Disease

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We have approached the role of cellular stress in neurodegenerative diseases caused by polyglutamine expansion (polyQ) in the context of Spinocerebellar ataxia type 7 (SCA7) that includes retinal degeneration. Using the R7E mouse, in which polyQ-ataxin-7 is specifically over-expressed in rod photoreceptors, we previously showed that rod dysfunction correlated to moderate and prolonged activation of the JNK/c-Jun stress pathway. SCA7 retinopathy was also associated with reduced expression of rod-specific genes, including the transcription factor Nrl, which is essential for rod differentiation and function. Here, we report that R7E retinopathy is improved upon breeding with the JunAA knock-in mice, in which JNK-mediated activation of c-Jun is compromised. Expression of Nrl and its downstream targets, which are involved in phototranduction, are partially restored in the JunAA-R7E mice. We further show that c-Jun can directly repress the transcription of Nrl. Our studies suggest that polyQ-induced cellular stress leads to repression of genes necessary for neuronal fate and function.

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“…Histologically, in agreement with a previous report (Grimm et al, 2001), retinas of JunAA mice were indistinguishable from CT retinas (Fig. 2, and data not shown).…”

Section: The Junaa Mutation Slows Down Segment Flattening By Polyq-atsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Preventing polyglutamine-induced activation of c-Jun delays neuronal dysfunction in a mouse model of SCA7 retinopathy

Mérienne¹,

Friedman²,

Akimoto³

et al. 2007

Neurobiology of Disease

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show abstract

“…Numerous reports from biochemical and functional studies have established that activation of JNK leads to increased c-Jun Ser-63 and Ser-73 phosphorylation and transcriptional activity (1, 6 -8, 17, 68). Results from a knock-in mouse model showed, however, that some biological functions of c-Jun did not require its N-terminal phosphorylation (12)(13)(14), indicating that JNK-c-Jun signaling transduction is not the only mechanism for regulating c-Jun activity. SuPr-1, a spliced form of SENP2, was recently identified as an activator of c-Jun independent of c-Jun phosphorylation (32).…”

Section: Fig 1 Senp1 Induces C-jundependent Transcriptionmentioning

confidence: 99%

“…Once activated, JNKs translocate to the nucleus, phosphorylate c-Jun at Ser-63 and Ser-73, and thereby enhance c-Jun transcriptional activity (3, 6, 8 -11). Although JNK-mediated c-Jun phosphorylation is a well documented mechanism for activating c-Jun-dependent transcription, studies with knock-in mice indicated that phosphorylation of c-Jun at Ser-63 and Ser-73 is not essential for some of the biological functions of c-Jun (12)(13)(14). These observations suggest that regulation of c-Jun transcriptional activity is complex and may occur at different levels.…”

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confidence: 99%

Differential Regulation of c-Jun-dependent Transcription by SUMO-specific Proteases

Cheng

Perkins

Yeh

2005

Journal of Biological Chemistry

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c-Jun is a transcription factor that plays an important role in regulating cell growth, apoptosis, differentiation, and transformation. The transcriptional activity of c-Jun can be regulated by both phosphorylation and sumoylation. It has also been shown that c-Jun transcription can be regulated by SuPr-1, an alternatively spliced form of SUMO-specific protease 2 (SENP2). However, the ability of SuPr-1 to enhance c-Jun transcription is dependent on promyelocytic leukemia but is independent of the desumoylation activity of SuPr-1. Here, we show that SUMOspecific protease 1 (SENP1) also markedly enhances the transcription activity of c-Jun. The action of SENP1 on c-Jun transcription is independent of the sumoylation and phosphorylation status of c-Jun but is critically dependent on the desumoylation activity of SENP1. We further show that p300 is essential for SENP1 to enhance c-Jun-dependent transcription because SENP1 can desumoylate the CRD1 domain of p300, thereby releasing the cis-repression of CRD1 on p300. Thus, two SUMO-specific proteases regulate c-Jun-dependent transcription through entirely different mechanisms.

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“…At the cellular level, a generalized role for many HOX proteins in cancer appears to be to prevent apoptosis by inhibiting cFos [24][25][26][27] and dual specificity protease 1 (DUSP1) expression [26,28,29] . DUSP1 is a tumour suppressor gene [30] , and whilst cFos is generally considered to be a protoncogene, cFos protein can also induce apoptosis through the activation of the cell death ligand, FAS1 [31][32][33][34][35] . Additional cellular functions of individual HOX proteins include DNA repair [36] and the regulation of the cell cycle [37] .…”

Section: The Hox Genesmentioning

confidence: 99%

HOX transcription factors and the prostate tumor microenvironment

Morgan¹,

Pandha²

2017

JCMT

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It is now well established that the tumor microenvironment plays an essential role in the survival, growth, invasion, and spread of cancer through the regulation of angiogenesis and localized immune responses. This review examines the role of the HOX genes, which encode a family of homeodomain-containing transcription factors, in the interaction between prostate tumors and their microenvironment. Previous studies have established that HOX genes have an important function in prostate cancer cell survival in vitro and in vivo, but there is also evidence that HOX proteins regulate the expression of genes in the cancer cell that influence the tumor microenvironment, and that cells in the microenvironment likewise express HOX genes that confer a tumor-supportive function. Here we provide an overview of these studies that, taken together, indicate that the HOX genes help mediate cross talk between prostate tumors and their microenvironment. Key words:Prostate cancer, tumor microenvironment, HOX, PBX, metastasis, angiogenesis ABSTRACTArticle history:

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AP-1 mediated retinal photoreceptor apoptosis is independent of N-terminal phosphorylation of c-Jun

Abstract: Apoptosis is essential for retinal development but it is also a major mode of cell loss in many human retinal dystrophies.

Cited by 37 publications

References 43 publications

Preventing polyglutamine-induced activation of c-Jun delays neuronal dysfunction in a mouse model of SCA7 retinopathy

Preventing polyglutamine-induced activation of c-Jun delays neuronal dysfunction in a mouse model of SCA7 retinopathy

Differential Regulation of c-Jun-dependent Transcription by SUMO-specific Proteases

HOX transcription factors and the prostate tumor microenvironment

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