NRL (neural retina leucine zipper) is a basic motif leucine zipper transcription factor of the Maf-subfamily. Multiple phosphorylated isoforms of NRL are detected specifically in rod photoreceptors. NRL regulates the expression of several rod-specific genes, including rhodopsin and cGMP phosphodiesterase beta-subunit, in synergy with other transcription factors (e.g. the homeodomain protein CRX). Missense mutations in the human NRL gene are associated with autosomal dominant retinitis pigmentosa, whereas the loss of its function leads to rodless retina in Nrl-knockout mice that exhibit enhanced S-cone function. To further elucidate the molecular mechanism(s) underlying NRL-mediated transcriptional regulation, we used yeast two-hybrid screening to isolate NRL-interacting proteins in the retina and report the identification of Flt3-interacting zinc-finger protein, Fiz1. Interaction of Fiz1 and NRL-leucine zipper was validated by GST pulldown assays and co-immunoprecipitation from bovine retinal nuclear extracts. Fiz1 suppressed NRL- but not CRX-mediated transactivation of rhodopsin promoter activity in transiently transfected CV1 cells. The mRNA and the protein for both Fiz1 and its only other known interacting protein Flt3, a receptor tyrosine kinase, are expressed in the retina. Our results indicate potential cross-talk among signaling pathways in the retina and suggest that the function of NRL is modulated by its interaction with specific repressor proteins.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/hmg/ddg035 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Degradome analysis to identify direct protein substrates of small-molecule degraders.
Cell Chem Biol
January 2025
German Cancer Research Center (DKFZ), Heidelberg, Germany; Heidelberg University, Medical Faculty, Heidelberg, Germany. Electronic address:
Article Synopsis
- - Targeted protein degradation (TPD) is a new method for selectively eliminating difficult-to-target proteins using small molecules, offering new therapeutic possibilities.
- - One major challenge is to clearly identify the primary targets of TPD, separate from secondary effects that occur elsewhere in the cell's protein landscape.
- - The researchers developed a mass spectrometry technique called DegMS that effectively analyzes protein degradation while controlling for changes in transcription and translation, demonstrated by studying various protein degraders and identifying FIZ1 as a target.
SARM1 regulates NAD-linked metabolism and select immune genes in macrophages.
J Biol Chem
February 2024
School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland. Electronic address:
Sterile alpha and HEAT/armadillo motif-containing protein (SARM1) was recently described as a NAD-consuming enzyme and has previously been shown to regulate immune responses in macrophages. Neuronal SARM1 is known to contribute to axon degeneration due to its NADase activity. However, how SARM1 affects macrophage metabolism has not been explored.
View Article and Find Full Text PDFExploring Somatic Alteration Associating With Aggressive Behaviors of Papillary Thyroid Carcinomas by Targeted Sequencing.
Front Oncol
October 2021
Department of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, Shanghai, China.
Wisely differentiating high-risk papillary thyroid carcinoma (PTC) patients from low-risk PTC patients preoperatively is necessary when comes to making a personalized treatment plan. It is not easy to stratify the risk of patients according to sonography or lab results before surgery. This study aims to seek out potential mutation gene markers that may be helpful in stratifying the risk of PTC.
View Article and Find Full Text PDFGenomic Classification and Prognosis in Acute Myeloid Leukemia.
N Engl J Med
June 2016
Cancer Genome Project, Wellcome Trust Sanger Institute (E.P., M.G., N.D.R., N.B., G.G., P.V.L., I.M., L.M., S.M., S.O., K.R., D.R.J., J.W.T., A.P.B., P.J.C.), and the European Bioinformatics Institute, European Molecular Biology Laboratory (EMBL-EBI) (M.G.), Hinxton, the Centre for Evolution and Cancer, Institute of Cancer Research, London (N.E.P., M.F.G.), and the Department of Haematology, University of Cambridge, Cambridge (N.B.) - all in the United Kingdom; the Departments of Epidemiology and Biostatistics and Cancer Biology, the Center for Molecular Oncology and the Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York (E.P.); the Department of Internal Medicine III, Ulm University, Ulm (L.B., V.I.G., P.P., K.D., R.F.S., H.D.), and the Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover (M.H., F.T., A.G.) - both in Germany; the Division of Hematology, Fondazione IRCCS, Istituto Nazionale dei Tumori, and Department of Oncology and Onco-Hematology, University of Milan, Milan (N.B.); the Department of Human Genetics, University of Leuven, Leuven, Belgium (P.V.L.); and the Department of Pathology, University of Otago, Christchurch, New Zealand (P.G., P.J.C.).
Background: Recent studies have provided a detailed census of genes that are mutated in acute myeloid leukemia (AML). Our next challenge is to understand how this genetic diversity defines the pathophysiology of AML and informs clinical practice.
Methods: We enrolled a total of 1540 patients in three prospective trials of intensive therapy.
Dissection of a novel autocrine signaling pathway via quantitative secretome and interactome mapping.
J Proteome Res
July 2014
Department of Cellular & Molecular Medicine and Ottawa Institute of Systems Biology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario K1H 8M5, Canada.
Epidermal homeostasis is a balancing act governed by a multitude of underlying regulatory events, and several growth factors and signaling pathways have been implicated in regulation of the balance between proliferation and differentiation in keratinocytes. We show here that the signal transducer/transcription factor FIZ1 (Flt3 interacting zinc finger protein-1) is a previously unknown player in this regulatory axis, promoting an increase in proliferation of HaCaT human immortalized keratinocytes that is driven by more rapid G1/S progression and mediated by activation of the MAP/ERK kinase pathway. Utilizing quantitative SILAC-based secretome analysis, we identified the insulin growth factor binding protein IGFBP3 as the key mediating factor, demonstrating that elevated FIZ1 levels promote increased IGFBP3 expression and secretion and a concurrent increased sensitivity to IGF1 signaling, while antibody-based neutralization of IGFBP3 abrogates the FIZ1-induced growth advantage.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!