Abstract
The bZIP transcription factor NFIL3 (Nuclear factor Interleukin 3 regulated, also known as E4 binding protein 4, E4BP4) regulates diverse biological processes from circadian rhythm to cellular viability. Recently, a host of novel roles have been identified for NFIL3 in immunological signal transduction, cancer, aging and metabolism. Elucidating the signaling pathways that are impacted by NFIL3 and the regulatory mechanisms that it targets, inhibits or activates will be critical for developing a clearer picture of its physiological roles in disease and normal processes. This review will discuss the recent advances and emerging issues regarding NFIL3-mediated transcriptional regulation of CEBPb and FOXO1 activated genes and signal transduction.
Highlights
Introduction2. NFIL3 is a b-ZIP Transcriptional Regulator 3
The NFIL3 transcriptional repressor impacts many cellular processes and is widely expressed in normal murine and human tissues[1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19]
In addition to the well characterized ability of NFIL3 to act in an anti-phase manner to DBP with reference to the circadian rhythm, NFIL3 is recurrently found to act in an antagonistic manner to CEBPβ7,13,15,20
Summary
The NFIL3 transcriptional repressor impacts many cellular processes and is widely expressed in normal murine and human tissues[1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19]. NFIL3 action opposes that of transcriptional activators by competing for access to target sites on DNA2,7,13,15,20-22. NFIL3 is commonly found within the context of feedback regulatory circuits[21]. The list of physiological roles for NFIL3 has evolved tremendously over the last few years. In addition to roles in circadian rhythm and B cell/neuronal survival, NFIL3 is implicated in having far reaching activities from immunological signal transduction to metabolism, aging and cancer[1,2,3,4,6,7,9,10,11,14,18,23,24]. We give an overview of NFIL3 transcriptional regulatory circuits and discuss emerging areas of NFIL3 research regarding cancer and diabetes
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