Phosphorylation inhibits DNA-binding of alternatively spliced aryl hydrocarbon receptor nuclear translocator

Journal Article · Fri Dec 09 04:00:00 EST 2005 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2005.0· OSTI ID:20793214

Kewley, Robyn J ^[1]; Whitelaw, Murray L ^[1]

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1. School of Molecular and Biomedical Science (Biochemistry), Centre for the Molecular Genetics of Development, University of Adelaide, SA 5005 (Australia)

The basic helix-loop-helix/PER-ARNT-SIM homology (bHLH/PAS) transcription factor ARNT (aryl hydrocarbon receptor nuclear translocator) is a key component of various pathways which induce the transcription of cytochrome P450 and hypoxia response genes. ARNT can be alternatively spliced to express Alt ARNT, containing an additional 15 amino acids immediately N-terminal to the DNA-binding basic region. Here, we show that ARNT and Alt ARNT proteins are differentially phosphorylated by protein kinase CKII in vitro. Phosphorylation had an inhibitory effect on DNA-binding to an E-box probe by Alt ARNT, but not ARNT, homodimers. This inhibitory phosphorylation occurs through Ser77. Moreover, a point mutant, Alt ARNT S77A, shows increased activity on an E-box reporter gene, consistent with Ser77 being a regulatory site in vivo. In contrast, DNA binding by an Alt ARNT/dioxin receptor heterodimer to the xenobiotic response element is not inhibited by phosphorylation with CKII, nor does Alt ARNT S77A behave differently from wild type Alt ARNT in the context of a dioxin receptor heterodimer.

• OSTI ID: 20793214
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 338; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
AMINO ACIDS
ANOXIA
DIOXIN
DNA
GENES
HYDROCARBONS
IN VITRO
IN VIVO
MUTANTS
PHOSPHORYLATION
RECEPTORS
TRANSCRIPTION
TRANSCRIPTION FACTORS