ARNT: A Key bHLH/PAS Regulatory Protein Across Multiple Pathways

Dougherty, Edward J.; Pollenz, Richard S.

doi:10.1016/b978-0-08-046884-6.00214-1

Cited by 9 publications

(12 citation statements)

References 184 publications

(198 reference statements)

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“…As mentioned previously, the class I bHLH/PAS proteins dimerize with class II members, to create a functional transcription factor complex, regulating the expression of genes under their control [4]. One of the most common class II representant is the aryl hydrocarbon receptor nuclear translocator (ARNT, HIF-1β), acting as a dimerization partner for several class I proteins: AHR, HIF family, SIM1 and SIM2 [86]. However, each heterodimeric complex cooperate with distinct cis-acting DNA elements, to regulate extremely different genes and pathways.…”

Section: Regulation Of the Subcellular Localization Of Class II Ofmentioning

confidence: 99%

“…However, each heterodimeric complex cooperate with distinct cis-acting DNA elements, to regulate extremely different genes and pathways. Therefore, ARNT participates in signal transduction pathways engaged in the xenobiotics metabolism, angiogenesis, vasculogenesis, hypoxia response and many various developmental processes [86]. Importantly, several ARNT variants have been identified in mammals: ARNT2, BMAL1 (ARNTL, ARNT3) and BMAL2 (ARNTL2, ARNT4).…”

Section: Regulation Of the Subcellular Localization Of Class II Ofmentioning

confidence: 99%

“…The defined bHLH and PAS domains are conserved in size and location between all proteins. However, all variants differ in the length of aa sequence [3], what results from a high divergence between their C-terminal parts [86]. Importantly, bHLH-PAS proteins C-termini are believed to be responsible for proteins function modulation and their activity regulation [2].…”

Section: Regulation Of the Subcellular Localization Of Class II Ofmentioning

confidence: 99%

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Subcellular Localization Signals of bHLH-PAS Proteins: Their Significance, Current State of Knowledge and Future Perspectives

Greb‐Markiewicz

Kolonko

2019

IJMS

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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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Section: Regulation Of the Subcellular Localization Of Class II Ofmentioning

confidence: 99%

Section: Regulation Of the Subcellular Localization Of Class II Ofmentioning

confidence: 99%

Section: Regulation Of the Subcellular Localization Of Class II Ofmentioning

confidence: 99%

See 1 more Smart Citation

Subcellular Localization Signals of bHLH-PAS Proteins: Their Significance, Current State of Knowledge and Future Perspectives

Greb‐Markiewicz

Kolonko

2019

IJMS

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“…In mammals there are at least three isoforms of HIF-α (HIF-1α, HIF-2α and HIF-3α) and two main isoforms of HIF-1β (ARNT1 and ARNT2). [11]. Interestingly, due to a genome duplication event, there are two paralogs for each of the three Hif-α isoforms (Hif-1αa, Hif-1αb, Hif-2αa, Hif-2αb, Hif-3αa and Hif-3αb) in zebrafish.…”

Section: Introductionmentioning

confidence: 99%

Bidirectional crosstalk between Hypoxia-Inducible Factor and glucocorticoid signalling in zebrafish larvae

et al. 2020

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In the last decades in vitro studies highlighted the potential for crosstalk between Hypoxia-Inducible Factor-(HIF) and glucocorticoid-(GC) signalling pathways. However, how this interplay precisely occurs in vivo is still debated. Here, we use zebrafish larvae (Danio rerio) to elucidate how and to what degree hypoxic signalling affects the endogenous glucocorticoid pathway and vice versa, in vivo. Firstly, our results demonstrate that in the presence of upregulated HIF signalling, both glucocorticoid receptor (Gr) responsiveness and endogenous cortisol levels are repressed in 5 days post fertilisation larvae. In addition, despite HIF activity being low at normoxia, our data show that it already impedes both glucocorticoid activity and levels. Secondly, we further analysed the in vivo contribution of glucocorticoids to HIF activity. Interestingly, our results show that both glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) play a key role in enhancing it. Finally, we found indications that glucocorticoids promote HIF signalling via multiple routes. Cumulatively, our findings allowed us to suggest a model for how this crosstalk occurs in vivo.

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“…It is constitutively expressed and acts as general heterodimerization partner for multiple class I members, including SIM1 [77] and NPAS4 [78,79]. In contrast to ARNT expressed equally in all tissues and interacting with wide spectrum of physiological partners (ARNT is indispensable for AHR and Hif signalling) [80], ARNT2 is highly expressed in brain (in the developing CNS), kidney, urinary tract and embryos [81] [82]. ARNT2 deficiency leads to the secondary microcephaly within the first few months of human life with a specific frontal and temporal lobe hypoplasia [83].…”

Section: Aryl Hydrocarbon Receptor Nuclear Translocator 2 (Arnt2) Andmentioning

confidence: 99%

The Participation of the Intrinsically Disordered Regions of the bHLH-PAS Transcription Factors in Disease Development

Greb‐Markiewicz¹,

Kolonko²

2020

Preprint

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The bHLH-PAS proteins are a family of transcription factors regulating expression of a wide range of genes involved in different functions, from differentiation and development control, by oxygen and toxins sensing to circadian clock setting. In addition to the well-preserved DNA-binding bHLH and PAS domains, bHLH-PAS proteins contain long intrinsically disordered C-terminal regions, responsible for their activity regulation. Our aim was to analyse the potential connection between disordered regions of the bHLH-PAS transcription factors with posttranscriptional modifications and liquid-liquid phase separation in the context of the disease-associated missense mutations. Highly flexible disordered regions, enriched in short more ordered motives, are responsible for wide spectrum of interactions with transcriptional co-regulators. Based on our in silico analysis and taking into account fact that transcription factors functions can be modulated by posttranslational modifications and spontaneous phase separation, we assume that the location of missense mutations inducing disease states, is clearly related to sequences directly undergoing these processes or to sequences responsible for their activity regulation.

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ARNT: A Key bHLH/PAS Regulatory Protein Across Multiple Pathways

Cited by 9 publications

References 184 publications

Subcellular Localization Signals of bHLH-PAS Proteins: Their Significance, Current State of Knowledge and Future Perspectives

Subcellular Localization Signals of bHLH-PAS Proteins: Their Significance, Current State of Knowledge and Future Perspectives

Bidirectional crosstalk between Hypoxia-Inducible Factor and glucocorticoid signalling in zebrafish larvae

The Participation of the Intrinsically Disordered Regions of the bHLH-PAS Transcription Factors in Disease Development

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