Investigation of Differential Post Transcriptional Regulation of 4E‐BP1 and 4E‐BP2 in Eukaryotic Cells Under Stress

Abstract

eIF4E‐binding proteins (eIF4E‐BPs or 4E‐BPs) are a family of proteins that inhibit the initiation of eukaryotic translation. They bind to eIF4E and inhibit the formation of eIF4F complex which is crucial for cap‐dependent translation initiation. There are 3 isotypes of 4E‐BPs, 4E‐BP1, 4E‐BP2 and 4E‐BP3. They are nearly 60% identical at the amino acid level. According to the NCBI reference sequences, 4E‐BP2 has a long 3′ UTR (6.8kb) whereas 4E‐BP1 (428 bp) and 4E‐BP3 (315 bp) do not. The presence of this relatively longer 3′ UTR could indicate the presence of cis‐acting regulatory elements (CREs) that are specific to 4E‐BP2. Under various cellular stress conditions, global translation is shut down to conserve energy. To examine the role of 3′ UTRs in promoting the availability of these 4E‐BPs, during stress, to decrease the cap‐dependent translation, 4E‐BP1 and 4E‐BP2 were both studied in relation to their gene expression (transcription and translation) under various stress conditions (ER stress, oxidative stress), cell cycle arrest and mTOR inhibition (conditions of growth arrest and inhibition, respectively). Under conditions of acute ER stress, 4E‐BP1 showed nearly 3‐fold increased expression than in control treatment (DMSO) whereas 4E‐BP2c and 4E‐BP3 did not show significant increase using qPCR. No changes in 4E‐BP1 protein levels (controls vs various conditions of stress) were detected whereas different 4E‐BP2 protein levels were seen under various conditions of cellular stress. Future studies will include investigation of promoter activity of these three gene products. The data suggests possible differential regulation of 4E‐BPs under cell stress condition.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.