Animal growth and development is dependent on reiterative use of key signaling pathways such as Hedgehog (Hh) pathway. It is widely believed that Cubitus-interruptus (Ci) mediates all functions of Hh pathway. Here we report that CG32062, the Drosophila homologue of Ataxin-2 Binding Protein 1 (dA2BP1), functions as a cofactor of Ci to specify intervein region between L3 and L4 veins of the adult wing. Specifically, Ci-mediated transactivation of knot/collier (kn) in this region of the developing wing imaginal disc is dependent on dA2BP1 function. Protein interaction studies and chromatin-immunoprecipiation experiments suggest that Ci helps dA2BP1 to bind kn promoter, which in turn may help Ci to activate kn expression. These results suggest a mechanism by which Ci may activate targets such as kn, which do not have classical Ci/Gli-binding sites.
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http://dx.doi.org/10.1016/j.ydbio.2010.02.039 | DOI Listing |
PLoS One
December 2024
Neuroscience, Merck Research Laboratories, Merck & Co., Inc., Rahway, New Jersey, United States of America.
Ataxin-2 is a protein containing a polyQ extension and intermediate length of polyQ extensions increases the risk of Amyotrophic Lateral Sclerosis (ALS). Down-regulation of Ataxin-2 has been shown to mitigate TDP-43 proteinopathy in ALS models. To identify alternative therapeutic targets that can mitigate TDP-43 toxicity, we examined the interaction between Ataxin-2 and TDP-43.
View Article and Find Full Text PDFStem Cell Res Ther
November 2024
School of Life Science and Biotechnology, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, 41566, Korea.
Genes Cells
December 2024
Laboratory of Molecular Cell Biology, Institute of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Pbp1, a yeast ortholog of human ataxin-2, is important for cell growth in the medium containing non-fermentable carbon sources. We had reported that Pbp1 regulates expression of genes related to glycogenesis via transcriptional regulation and genes related to mitochondrial function through mRNA stability control. To further analyze the role of Pbp1 in gene expression, we first examined the time course of gene expression after transfer from YPD medium containing glucose to YPGlyLac medium containing glycerol and lactate.
View Article and Find Full Text PDFDev Cell
October 2024
Department of Pathology, Yale School of Medicine, New Haven, CT 06510, USA; Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT 06510, USA; Program in Cellular Neuroscience, Neurodegeneration, and Repair, Yale School of Medicine, New Haven, CT 06510, USA. Electronic address:
Altered RNA metabolism and misregulation of transactive response DNA-binding protein of 43 kDa (TDP-43), an essential RNA-binding protein (RBP), define amyotrophic lateral sclerosis (ALS). Intermediate-length polyglutamine (polyQ) expansions of Ataxin-2, a like-Sm (LSm) RBP, are associated with increased risk for ALS, but the underlying biological mechanisms remain unknown. Here, we studied the spatiotemporal dynamics and mRNA regulatory functions of TDP-43 and Ataxin-2 ribonucleoprotein (RNP) condensates in rodent (rat) primary cortical neurons and mouse motor neuron axons in vivo.
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