Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 20, Issue 19, Pages -Publisher
MDPI
DOI: 10.3390/ijms20194746
Keywords
ARNT; BMAL; bHLH-PAS; CLOCK; CYCLE; GCE; HIF; MET; NPAS; NLS; NES; nucleocytoplasmic shuttling; SIM; SIMA; TANGO
Funding
- National Science Centre (NCN): PRELUDIUM pre-doctoral grant [UMO-2017/27/N/NZ1/01783]
- National Science Centre (NCN): ETIUDA doctoral scholarship [UMO-2018/28/T/NZ1/00337]
- Polish Ministry of Science and Higher Education for the Wroclaw University of Science and Technology, Faculty of Chemistry [0401/0143/18]
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The bHLH-PAS (basic helix-loop-helix/ Period-ARNT-Single minded) proteins are a family of transcriptional regulators commonly occurring in living organisms. bHLH-PAS members act as intracellular and extracellular signals sensors, initiating response to endo- and exogenous signals, including toxins, redox potential, and light. The activity of these proteins as transcription factors depends on nucleocytoplasmic shuttling: the signal received in the cytoplasm has to be transduced, via translocation, to the nucleus. It leads to the activation of transcription of particular genes and determines the cell response to different stimuli. In this review, we aim to present the current state of knowledge concerning signals that affect shuttling of bHLH-PAS transcription factors. We summarize experimentally verified and published nuclear localization signals/nuclear export signals (NLSs/NESs) in the context of performed in silico predictions. We have used most of the available NLS/NES predictors. Importantly, all our results confirm the existence of a complex system responsible for protein localization regulation that involves many localization signals, which activity has to be precisely controlled. We conclude that the current stage of knowledge in this area is still not complete and for most of bHLH-PAS proteins an experimental verification of the activity of further NLS/NES is needed.
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