| Gene information | Literature | Expression | lncRNA | Mutation | Homolog |
Basic Information | |
|---|---|
Gene ID | 8725 |
Name | URI1 |
Synonymous | URI1, prefoldin-like chaperone;URI1;URI1, prefoldin-like chaperone |
Definition | RNA polymerase II subunit 5-mediating protein|RPB5-mediating protein|protein phosphatase 1 regulatory subunit 19|protein phosphatase 1, regulatory subunit 19|unconventional prefoldin RPB5 interactor 1 |
Position | 19q12 |
Gene type | protein-coding |
Title | Abstract |
| A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene. | Oncogenic mutations in the small GTPase Ras are highly prevalent in cancer, but an understanding of the vulnerabilities of these cancers is lacking. We undertook a genome-wide RNAi screen to identify synthetic lethal interactions with the KRAS oncogene. We discovered a diverse set of proteins whose depletion selectively impaired the viability of Ras mutant cells. Among these we observed a strong enrichment for genes with mitotic functions. We describe a pathway involving the mitotic kinase PLK1, the anaphase-promoting complex/cyclosome, and the proteasome that, when inhibited, results in prometaphase accumulation and the subsequent death of Ras mutant cells. Gene expression analysis indicates that reduced expression of genes in this pathway correlates with increased survival of patients bearing tumors with a Ras transcriptional signature. Our results suggest a previously underappreciated role for Ras in mitotic progression and demonstrate a pharmacologically tractable pathway for the potential treatment of cancers harboring Ras mutations. |
| URI is an oncogene amplified in ovarian cancer cells and is required for their survival. | Abrogation of negative feedback control represents a fundamental requirement for aberrantly activated signaling pathways to promote malignant transformation and resistance to therapy. Here we identify URI, which encodes a mitochondrial inhibitor of PP1gamma and PP1gamma-mediated feedback inhibition of S6K1-BAD survival signaling, as an oncogene amplified and overexpressed in ovarian cancer cell lines and human ovarian carcinomas. URI is an "addicting" oncogene selectively required for the survival of ovarian cancer cells with increased URI copy number. By constitutively detaining PP1gamma in inactive complexes, URI sustains S6K1 survival signaling under growth factor-limiting conditions and mediates resistance of cells to cisplatin. Thus, oncogenic activation of URI defines an important mechanism for activating mitochondrial S6K1-BAD signaling and promoting cell survival through disabling PP1gamma-dependent negative feedback inhibition. |