scholarly journals Two Murine Homologs of theDrosophilaSingle-minded Protein That Interact with the Mouse Aryl Hydrocarbon Receptor Nuclear Translocator Protein

1997 ◽  
Vol 272 (7) ◽  
pp. 4451-4457 ◽  
Author(s):  
Markus R. Probst ◽  
Chen-Ming Fan ◽  
Marc Tessier-Lavigne ◽  
Oliver Hankinson
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Translocator Protein ◽  
Aryl Hydrocarbon

Identification of functional domains of the aryl hydrocarbon receptor nuclear translocator protein (ARNT)

1994 ◽  
Vol 14 (9) ◽  
pp. 6075-6086
Author(s):  
S Reisz-Porszasz ◽  
M R Probst ◽  
B N Fukunaga ◽  
O Hankinson
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Mutant Cell ◽  
Translocator Protein ◽  
Functional Domains ◽  
Recognition Sequence ◽  
Dimerization Domain ◽  
Alpha Helices ◽  
Helix Loop Helix ◽  
Aryl Hydrocarbon

The activated aryl hydrocarbon receptor (AHR) and the AHR nuclear translocator (ARNT) bind DNA as a heterodimer. Both proteins represent a novel class of basic helix-loop-helix (bHLH)-containing transcription factors in that (i) activation of AHR requires the binding of ligand (e.g., 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD]), (ii) the xenobiotic responsive element (XRE) recognized by the AHR/ARNT heterodimer differs from the recognition sequence for nearly all other bHLH proteins, and (iii) both proteins contain a PAS homology region, which in the Drosophila PER and SIM proteins functions as a dimerization domain. A cDNA for mouse ARNT has been cloned, and potential functional domains of ARNT were investigated by deletion analysis. A mutant lacking all regions of ARNT other than the bHLH and PAS regions is unimpaired in TCDD-dependent dimerization and subsequent XRE binding and only modestly reduced in ability to complement an ARNT-deficient mutant cell line, c4, in vivo. Both the first and second alpha helices of the bHLH region are required for dimerization. The basic region is required for XRE binding but not for dimerization. Deletion of either the A or B segments of the PAS region slightly affects TCDD-induced heterodimerization, while deletion of the complete PAS region severely affects (but does not eliminate) dimerization. Thus, ARNT possesses multiple domains required for maximal heterodimerization. Mutants deleted for PAS A, PAS B, and the complete PAS region all retain some degree of XRE binding, yet none can rescue the c4 mutant. Therefore, both the PAS A and PAS B segments, besides contributing to dimerization, apparently fulfill additional, unknown functions required for biological activity of ARNT.

scholarly journals Identification of functional domains of the aryl hydrocarbon receptor nuclear translocator protein (ARNT).

1994 ◽  
Vol 14 (9) ◽  
pp. 6075-6086 ◽  
Author(s):  
S Reisz-Porszasz ◽  
M R Probst ◽  
B N Fukunaga ◽  
O Hankinson
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Mutant Cell ◽  
Translocator Protein ◽  
Functional Domains ◽  
Recognition Sequence ◽  
Dimerization Domain ◽  
Alpha Helices ◽  
Helix Loop Helix ◽  
Aryl Hydrocarbon

The activated aryl hydrocarbon receptor (AHR) and the AHR nuclear translocator (ARNT) bind DNA as a heterodimer. Both proteins represent a novel class of basic helix-loop-helix (bHLH)-containing transcription factors in that (i) activation of AHR requires the binding of ligand (e.g., 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD]), (ii) the xenobiotic responsive element (XRE) recognized by the AHR/ARNT heterodimer differs from the recognition sequence for nearly all other bHLH proteins, and (iii) both proteins contain a PAS homology region, which in the Drosophila PER and SIM proteins functions as a dimerization domain. A cDNA for mouse ARNT has been cloned, and potential functional domains of ARNT were investigated by deletion analysis. A mutant lacking all regions of ARNT other than the bHLH and PAS regions is unimpaired in TCDD-dependent dimerization and subsequent XRE binding and only modestly reduced in ability to complement an ARNT-deficient mutant cell line, c4, in vivo. Both the first and second alpha helices of the bHLH region are required for dimerization. The basic region is required for XRE binding but not for dimerization. Deletion of either the A or B segments of the PAS region slightly affects TCDD-induced heterodimerization, while deletion of the complete PAS region severely affects (but does not eliminate) dimerization. Thus, ARNT possesses multiple domains required for maximal heterodimerization. Mutants deleted for PAS A, PAS B, and the complete PAS region all retain some degree of XRE binding, yet none can rescue the c4 mutant. Therefore, both the PAS A and PAS B segments, besides contributing to dimerization, apparently fulfill additional, unknown functions required for biological activity of ARNT.

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