RNAi screen reveals synthetic lethality between cyclin G-associated kinase and FBXW7 by inducing aberrant mitoses.

ABSTRACT:

Background

F-box and WD40 repeat domain-containing 7 (FBXW7) is an E3 ubiquitin ligase involved in the ubiquitination and degradation of multiple oncogenic substrates. The tumour suppressor function is frequently lost in multiple cancers through genetic deletion and mutations in a broad range of tumours. Loss of FBXW7 functionality results in the stabilisation of multiple major oncoproteins, culminating in increased cellular proliferation and pro-survival pathways, cell cycle deregulation, chromosomal instability and altered metabolism. Currently, there is no therapy to specifically target FBXW7-deficient tumours.

Methods

We performed a siRNA kinome screen to identify synthetically lethal hits to FBXW7 deficiency.

Results

We identified and validated cyclin G-associate

SUBMITTER: Dolly SO 

PROVIDER: S-EPMC5625678 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature