Project description:This SuperSeries is composed of the following subset Series: GSE17162: Structural and Functional Analysis of Viral siRNAs using Solexa sequencing GSE17164: Structural and Functional Analysis of Viral siRNAs using 454 sequencing Refer to individual Series
Project description:Supporting microarray data for manuscript entitled "OSTEOPONTIN AND PAI-1 EXPRESSION IN MALIGNANT HYPERTENSION: SUPPRESSION BY p38 MAPK INHIBITORS" submitted to the HYPERTENSION journal. Keywords: timecourse, diet
Project description:This PXD project contains two projects published on ProteomicsDB (https://www.proteomicsDB.org) as integral part of the publication. The first project entitled 'human body map' (https://www.proteomicsdb.org/#projects/42) involves the analysis of 36 different human tissues and body fluids. The second project entitled 'Cellzome adopted' includes a collection of raw files which comprises identifications of 'missing proteins'.
Project description:Quantitative proteomic analysis raw data for the manuscript entitled “A covalent peptide-based lysosome-targeting protein degradation platform for cancer immunotherapy”.
Project description:Whole-genome tiling arrays were used to validate deletions and tandem duplications that were inferred based on next-generation sequencing data. The arrays were generated for six samples of the Drosophila melanogaster Genetic Reference Panel (DGRP) as well as the Berkeley reference strain. Structural variations (SVs) were assessed by comparing probe intensities within the region of interest between the sample for which the SV was predicted and the reference strain.
Project description:The MYC is a oncogenic driver in diverse human cancers. However, its intrinsically disordered structure has precluded direct pharmacological inhibition, posing a major challenge to targeting MYC-driven malignancies. This limitation has prompted the search for alternative strategies to modulate MYC activity. Recent findings suggest that MYC engage with cellular RNAs, revealing a previously underappreciated layer of regulatory control. Here, we identify the long noncoding RNA NEAT1_1 as a component of a MYC–NEAT1_1 protein–RNA complex that modulates MYC protein stability. While NEAT1 knockdown moderately increases MYC levels, we hypothesized that its structural conformation is critical to this regulatory function. To test this, we designed 88 antisense oligonucleotide mixmers targeting distinct structural regions of NEAT1_1. This screen uncovered both MYC-destabilizing and MYC-stabilizing oligonucleotides, without altering NEAT1_1 expression levels. A focused CRISPR screen identified UBR5 as an E3 ligase required for MYC-destabilizing mixmers induced MYC degradation, and we validated that these mixmers enhanced the MYC–UBR5 interaction, leading to more polyubiquitination of MYC. Our findings highlight a structure-guided mechanism by which a scaffold lncRNA governs the stability of an otherwise undruggable oncogene. This study provides proof-of-concept that RNA structural modulation can rewire protein turnover pathways, offering a promising therapeutic avenue for MYC-driven cancers.
Project description:The MYC is a oncogenic driver in diverse human cancers. However, its intrinsically disordered structure has precluded direct pharmacological inhibition, posing a major challenge to targeting MYC-driven malignancies. This limitation has prompted the search for alternative strategies to modulate MYC activity. Recent findings suggest that MYC engage with cellular RNAs, revealing a previously underappreciated layer of regulatory control. Here, we identify the long noncoding RNA NEAT1_1 as a component of a MYC–NEAT1_1 protein–RNA complex that modulates MYC protein stability. While NEAT1 knockdown moderately increases MYC levels, we hypothesized that its structural conformation is critical to this regulatory function. To test this, we designed 88 antisense oligonucleotide mixmers targeting distinct structural regions of NEAT1_1. This screen uncovered both MYC-destabilizing and MYC-stabilizing oligonucleotides, without altering NEAT1_1 expression levels. A focused CRISPR screen identified UBR5 as an E3 ligase required for MYC-destabilizing mixmers induced MYC degradation, and we validated that these mixmers enhanced the MYC–UBR5 interaction, leading to more polyubiquitination of MYC. Our findings highlight a structure-guided mechanism by which a scaffold lncRNA governs the stability of an otherwise undruggable oncogene. This study provides proof-of-concept that RNA structural modulation can rewire protein turnover pathways, offering a promising therapeutic avenue for MYC-driven cancers.
Project description:The MYC is a oncogenic driver in diverse human cancers. However, its intrinsically disordered structure has precluded direct pharmacological inhibition, posing a major challenge to targeting MYC-driven malignancies. This limitation has prompted the search for alternative strategies to modulate MYC activity. Recent findings suggest that MYC engage with cellular RNAs, revealing a previously underappreciated layer of regulatory control. Here, we identify the long noncoding RNA NEAT1_1 as a component of a MYC–NEAT1_1 protein–RNA complex that modulates MYC protein stability. While NEAT1 knockdown moderately increases MYC levels, we hypothesized that its structural conformation is critical to this regulatory function. To test this, we designed 88 antisense oligonucleotide mixmers targeting distinct structural regions of NEAT1_1. This screen uncovered both MYC-destabilizing and MYC-stabilizing oligonucleotides, without altering NEAT1_1 expression levels. A focused CRISPR screen identified UBR5 as an E3 ligase required for MYC-destabilizing mixmers induced MYC degradation, and we validated that these mixmers enhanced the MYC–UBR5 interaction, leading to more polyubiquitination of MYC. Our findings highlight a structure-guided mechanism by which a scaffold lncRNA governs the stability of an otherwise undruggable oncogene. This study provides proof-of-concept that RNA structural modulation can rewire protein turnover pathways, offering a promising therapeutic avenue for MYC-driven cancers.