ArticleThe Journal of biological chemistry2010
Sumoylation of bZIP transcription factor NRL modulates target gene expression during photoreceptor differentiation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 43 citations in OpenAlex.
- Molecular mechanisms controlling vertebrate retinal patterning, neurogenesis, and cell fate specification.Trends in genetics : TIG · 2023Review
- SUMO1-regulated DBC1 promotes p53-dependent stress-induced apoptosis of lens epithelial cells.Aging · 2023Article
- Protein kinase CK2 modulates the activity of Maf-family bZIP transcription factor NRL in rod photoreceptors of mammalian retina.Human molecular genetics · 2023Article
- Influence of Sox protein SUMOylation on neural development and regeneration.Neural regeneration research · 2022Review
- The E3 Ligase PIAS1 Regulates p53 Sumoylation to Control Stress-Induced Apoptosis of Lens Epithelial Cells Through the Proapoptotic Regulator Bax.Frontiers in cell and developmental biology · 2021Article
- Article
- Molecular signature for senile and complicated cataracts derived from analysis of sumoylation enzymes and their substrates in human cataract lenses.Aging cell · 2020Article
- Targeted deletion of an NRL- and CRX-regulated alternative promoter specifically silences FERM and PDZ domain containing 1 (Frmpd1) in rod photoreceptors.Human molecular genetics · 2019Article
- Expression of deubiquitinating enzyme genes in the developing mammal retina.Molecular vision · 2019Article
- Pias3 is necessary for dorso-ventral patterning and visual response of retinal cones but is not required for rod photoreceptor differentiation.Biology open · 2017Article
- Novel Regulatory Mechanisms for the SoxC Transcriptional Network Required for Visual Pathway Development.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Mechanisms of Photoreceptor Patterning in Vertebrates and Invertebrates.Trends in genetics : TIG · 2016Review
- Article
- Feedback induction of a photoreceptor-specific isoform of retinoid-related orphan nuclear receptor β by the rod transcription factor NRL.The Journal of biological chemistry · 2014Article
- Neuronal SUMOylation: mechanisms, physiology, and roles in neuronal dysfunction.Physiological reviews · 2014Review
- The transcription-splicing protein NonO/p54nrb and three NonO-interacting proteins bind to distal enhancer region and augment rhodopsin expression.Human molecular genetics · 2014Article
- OTX2 loss causes rod differentiation defect in CRX-associated congenital blindness.The Journal of clinical investigation · 2014Article
- Protein sumoylation in brain development, neuronal morphology and spinogenesis.Neuromolecular medicine · 2013Review
- Conditional knockdown of DNA methyltransferase 1 reveals a key role of retinal pigment epithelium integrity in photoreceptor outer segment morphogenesis.Development (Cambridge, England) · 2013Article
- Reprogramming amacrine and photoreceptor progenitors into retinal ganglion cells by replacing Neurod1 with Atoh7.Development (Cambridge, England) · 2013Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Development of rod photoreceptors in the mammalian retina is critically dependent on the basic motif-leucine zipper transcription factor NRL (neural retina leucine zipper). In the absence of NRL, photoreceptor precursors in mouse retina produce only cones that primarily express S-opsin. Conversely, ectopic expression of NRL in post-mitotic precursors leads to a rod-only retina. To explore the role of signaling molecules in modulating NRL function, we identified putative sites of post-translational modification in the NRL protein by in silico analysis. Here, we demonstrate the sumoylation of NRL in vivo and in vitro, with two small ubiquitin-like modifier (SUMO) molecules attached to the Lys-20 residue. NRL-K20R and NRL-K20R/K24R sumoylation mutants show reduced transcriptional activation of Nr2e3 and rhodopsin promoters (two direct targets of NRL) in reporter assays when compared with wild-type NRL. Consistent with this, in vivo electroporation of the NRL-K20R/K24R mutant into newborn Nrl(-/-) mouse retina leads to reduced Nr2e3 activation and only a partial rescue of the Nrl(-/-) phenotype in contrast to the wild-type NRL that is able to convert cones to rod photoreceptors. Although PIAS3 (protein inhibitor of activated STAT3), an E3-SUMO ligase implicated in photoreceptor differentiation, can be immunoprecipitated with NRL, there appears to be redundancy in E3 ligases, and PIAS3 does not seem to be essential for NRL sumoylation. Our studies suggest an important role of sumoylation in fine-tuning the activity of NRL and thereby incorporating yet another layer of control in gene regulatory networks involved in photoreceptor development and homeostasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.