GenomeRNAi - a database for RNAi phenotypes and reagents
TitleScreen TitleAssayBiomodelSpecies
A systematic RNAi synthetic interaction screen reveals a link between p53 and snoRNP assembly. Krastev et al. (2011) TP53 interactions (2) TP53 protein expressionHCT116 ( wildtype and TP53 knockout)H. sapiens

Abstract

TP53 (tumour protein 53) is one of the most frequently mutated genes in human cancer and its role during cellular transformation has been studied extensively. However, the homeostatic functions of p53 are less well understood. Here, we explore the molecular dependency network of TP53 through an RNAi-mediated synthetic interaction screen employing two HCT116 isogenic cell lines and a genome-scale endoribonuclease-prepared short interfering RNA library. We identify a variety of TP53 synthetic interactions unmasking the complex connections of p53 to cellular physiology and growth control. Molecular dissection of the TP53 synthetic interaction with UNRIP indicates an enhanced dependency of TP53-negative cells on small nucleolar ribonucleoprotein (snoRNP) assembly. This dependency is mediated by the snoRNP chaperone gene NOLC1 (also known as NOPP140), which we identify as a physiological p53 target gene. This unanticipated function of TP53 in snoRNP assembly highlights the potential of RNAi-mediated synthetic interaction screens to dissect molecular pathways of tumour suppressor genes.

Screen details


Stable Id: GR00196-A-2
Screen title: TP53 interactions (2)
Assay: TP53 protein expression
Method: Fluorescence
Scope: Selected genes
Screen type: Cell-based
Species: Homo sapiens
Biosource: Cell line
Biomodel: HCT116 ( wildtype and TP53 knockout)
Library: Custom-made, Custom-made
Reagent type: esiRNA
Score type: Z-score
Cutoff: np
Notes: