Protein-protein interaction via PAS domains: role of the PAS domain in positive and negative regulation of the bHLH/PAS dioxin receptor-Arnt transcription factor complex.

Lindebro, Maria C; Poellinger, Lorenz; Whitelaw, Murray L.

doi:10.1002/j.1460-2075.1995.tb07359.x

Cited by 175 publications

(155 citation statements)

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“…phosphorylation-deficient mutant phyA). Our data clearly showed that the phosphorylation of phyA influences the protein-protein interaction between phyA and its putative signal transducers, NDPK2 and PIF3, whose binding sites are near to the hinge region and to PER-ARNT-SIM-related domains implicated in mediating protein-protein interaction in other systems (Lindebro et al, 1995;Choi et al, 1999;Zhu et al, 2000). Another phytochrome-interacting protein, PKS1, which is known to bind the His kinase-related domain at the C-terminal end region , normally bound with phosphorylated phyA (data not shown).…”

Section: Discussionmentioning

confidence: 61%

Phytochrome Phosphorylation Modulates Light Signaling by Influencing the Protein–Protein Interaction[W]

et al. 2004

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Plant photoreceptor phytochromes are phosphoproteins, but the question as to the functional role of phytochrome phosphorylation has remained to be elucidated. We investigated the functional role of phytochrome phosphorylation in plant light signaling using a Pfr-specific phosphorylation site mutant, Ser598Ala of oat (Avena sativa) phytochrome A (phyA). The transgenic Arabidopsis thaliana (phyA-201 background) plants with this mutant phyA showed hypersensitivity to light, suggesting that phytochrome phosphorylation at Serine-598 (Ser598) in the hinge region is involved in an inhibitory mechanism. The phosphorylation at Ser598 prevented its interaction with putative signal transducers, Nucleoside Diphosphate Kinase-2 and Phytochrome-Interacting Factor-3. These results suggest that phosphorylation in the hinge region of phytochromes serves as a signal-modulating site through the protein–protein interaction between phytochrome and its putative signal transducer proteins.

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Section: Discussionmentioning

confidence: 61%

Phytochrome Phosphorylation Modulates Light Signaling by Influencing the Protein–Protein Interaction[W]

et al. 2004

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“…Empty pcDNA3.1 plasmid (Invitrogen) was used as a negative control for mock transfection. Plasmid containing full-length HIF-1β (pARNT/GEM7) was provided kindly by Prof. L. Poellinger, Karolinska Institute, Stockholm, Sweden [Lindebro et al, 1995]. Empty pCMV (Genlantis, San Diego, CA) vector was used as a negative control.…”

Section: Page 6 Of 30mentioning

confidence: 99%

Role of the HBx oncoprotein in carbonic anhydrase 9 induction

Holotnakova¹,

Tylková²,

Takáčová³

et al. 2009

Journal of Medical Virology

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International audienceCarbonic anhydrase 9 (CA9), as one of the most hypoxia-responsive genes, has been associated almost exclusively with hypoxic tumours. Its principal role is in pH regulation which helps tumour cells overcome intracellular acidosis and survive extended periods of time with low oxygen. Hypoxia-inducible factor 1 (HIF-1) is the main transcriptional activator of CA9. Hepatitis B virus X protein (HBx) has been shown to increase the transcriptional activity of HIF-1. HBx is often expressed from the gene integrated in the hepatocytes infected persistently and contributes significantly to alterations in host gene expression that can lead to the development of hepatocellular carcinoma (HCC) associated with HBV. The aim of this study was to determine the effect of HBx on expression of CA9. Transient transfection of HBx led to an increase in the expression of CA9 as assessed by RT-PCR and Western blotting. HBx was able to increase CA9 promoter activity significantly in several cell lines. The effect was mediated via HIF-1 and a functional HRE element located –10/–3 bp upstream of the CA9 transcription initiation site. These data suggest that CA9 may be involved in the development of HCC by contributing to the survival of hepatocytes infected with HBV in liver tissue with fibrosis

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“…We have previously demonstrated that the PAS domain of the dioxin receptor can function as a dimerization interface independently of the bHLH domain in a hybrid-protein interaction assay in mammalian cells (15). Furthermore, the C-terminal half of the PAS domain located between amino acids 230 and 421 and containing the minimal LBD spanning the PAS B motif has been shown to be essential for the PAS-mediated interaction with Arnt (15). We therefore examined the dimerization and DNA-binding activities of the dioxin receptor deletion mutant DR⌬PASB, lacking the minimal PAS B motif encompassed by amino acids 288 -421, but maintaining the N-terminal half of the LBD including the PAS A motif (Fig.…”

Section: Definition Of a Dioxin Receptor Deletion Mutant That Shows Bmentioning

confidence: 99%

“…Contiguous to the amino-terminal bHLH DNA-binding and dimerization motifs, members of this subfamily are identified on the basis of a second region of homology, the PAS (Per-Arnt-Sim) domain, originally identified in the Drosophila proteins PER and SIM, and Arnt. The PAS domain encompasses a region of ϳ250 -300 amino acids harboring two degenerate repeat sequences of 44 amino acids termed PAS A and PAS B, respectively, and has been shown to constitute an additional dimerization interface that can function independently of the bHLH motif (14,15). More recently, additional roles in the regulation of heterodimerization and DNA binding specificities have been attributed to the PAS domain (16,17).…”

mentioning

confidence: 99%

Definition of a Dioxin Receptor Mutant That Is a Constitutive Activator of Transcription

McGuire

Okamoto

Whitelaw

et al. 2001

Journal of Biological Chemistry

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The intracellular dioxin (aryl hydrocarbon) receptor is a ligand-activated transcription factor that mediates the adaptive and toxic responses to environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin and structurally related congeners. Whereas the ligand-free receptor is characterized by its association with the molecular chaperone hsp90, exposure to ligand initiates a multistep activation process involving nuclear translocation, dissociation from the hsp90 complex, and dimerization with its partner protein Arnt. In this study, we have characterized a dioxin receptor deletion mutant lacking the minimal ligand-binding domain of the receptor. This mutant did not bind ligand and localized constitutively to the nucleus. However, this protein was functionally inert since it failed to dimerize with Arnt and to bind DNA. In contrast, a dioxin receptor deletion mutant lacking the minimal PAS B motif but maintaining the N-terminal half of the ligand-binding domain showed constitutive dimerization with Arnt, bound DNA, and activated transcription in a ligand-independent manner. Interestingly, this mutant showed a more potent functional activity than the dioxin-activated wild-type receptor in several different cell lines. In conclusion, the constitutively active dioxin receptor may provide an important mechanistic tool to investigate receptor-mediated regulatory pathways in closer detail.The intracellular dioxin receptor also known as the aryl hydrocarbon receptor, is a ligand-dependent transcription factor that mediates the biological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 1 commonly known as dioxin (1). Although disruption of the dioxin receptor gene in mice has not yielded conclusive results, it remains a possible scenario that physiological mechanisms may exist for activation of receptor function, e.g. during critical stages of vertebrate development (2-5). However, an endogenous ligand for the receptor has not yet been identified, suggesting that alternative pathways for receptor activation may exist.In the absence of ligand, the dioxin receptor is generally found in the cytoplasm associated in high molecular weight complexes comprising a dimer of the molecular chaperone hsp90, an immunophilin homolog known as XAP2 (hepatitis B virus X-associated protein-2)/AIP (aryl hydrocarbon receptorinteracting protein)/ARA9 (aryl hydrocarbon receptor-associated protein-9), and the co-chaperone p23 (6 -11). In the presence of dioxin, the receptor is converted to a functional DNAbinding species in a multistep process involving nuclear translocation, dissociation from the hsp90 complex, and dimerization with its partner protein Arnt (Ah receptor nuclear translocator). Formation of the dioxin receptor/Arnt heterodimer is a prerequisite for DNA binding and promotes transcription of target genes including those encoding xenobioticmetabolizing enzymes such as CYP1A1 (1). Both the dioxin receptor and Arnt are members of a distinct subclass of the basic helix-loop-helix (bHLH) family of transcriptional regul...

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Protein-protein interaction via PAS domains: role of the PAS domain in positive and negative regulation of the bHLH/PAS dioxin receptor-Arnt transcription factor complex.

Cited by 175 publications

References 46 publications

Phytochrome Phosphorylation Modulates Light Signaling by Influencing the Protein–Protein Interaction[W]

Phytochrome Phosphorylation Modulates Light Signaling by Influencing the Protein–Protein Interaction[W]

Role of the HBx oncoprotein in carbonic anhydrase 9 induction

Definition of a Dioxin Receptor Mutant That Is a Constitutive Activator of Transcription

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