The role of Arf tumor suppressor in translational reprogramming

NIH RePORTER · NIH · F32 · $65,310 · view on reporter.nih.gov ↗

Abstract

ABSTRACT The ARF tumor suppressor is frequently mutated or downregulated in cancer. The major role of ARF is to activate p53 by sequestering the p53 regulator Mdm2. ARF also plays a significant role in ribosome biogenesis and mRNA translation. Previously, loss of Arf has been shown to cause a bulk increase in ribosome biogenesis, ribosome export into the cytoplasm and an increase in global protein synthesis. Activation of ARF inhibits these processes. Notably, ARF is known to specifically regulate the translation of several mRNAs. Based on previously published data we hypothesize that ARF regulates the translation of IRES containing mRNAs through displacement of RpL11 from the ribosome. To address our hypothesis, we propose three aims: 1) To map global translational regulation upon ARF loss or gain using ribosome profiling. 2) To assess the regulation of IRES containing mRNAs by ARF. 3) To identify proteins involved in ARF- dependent translational reprogramming

Key facts

NIH application ID
9894641
Project number
5F32GM131514-02
Recipient
WASHINGTON UNIVERSITY
Principal Investigator
Kyle Cottrell
Activity code
F32
Funding institute
NIH
Fiscal year
2020
Award amount
$65,310
Award type
5
Project period
2019-03-01 → 2021-02-28