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.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Krastev DB,Slabicki M,Paszkowski-Rogacz M,Hubner NC,Junqueira M,Shevchenko A,Mann M,Neugebauer KM,Buchholz Fdoi
10.1038/ncb2264subject
Has Abstractpub_date
2011-06-05 00:00:00pages
809-18issue
7eissn
1465-7392issn
1476-4679pii
ncb2264journal_volume
13pub_type
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