A Similar DNA-binding Motif in NFAT Family Proteins and the Rel Homology Region

Jugnu Jain,Emmanuel Burgeon,Tina M Badalian,Patrick G Hogan,Anjana Rao

doi:10.1074/jbc.270.8.4138

Jugnu Jain, Emmanuel Burgeon + Show 3 more

Open Access

https://doi.org/10.1074/jbc.270.8.4138

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Abstract

The cyclosporin-sensitive factor NFATp cooperates with Fos and Jun family proteins to regulate transcription of the interleukin 2 gene in activated T cells. We have defined a 187-amino-acid fragment of NFATp, located centrally within the protein sequence, as the minimal region required for DNA binding and for complex formation with Fos and Jun. The sequence of this region of NFATp shows a low degree of similarity to the Rel homology region. One specific short sequence in NFATp (RAHYETEG), located near the NH2 terminus of the DNA-binding domain, resembles a highly conserved sequence (RFRYxCEG) that is located near the NH2 terminus of the Rel homology region and that has been implicated in DNA binding by Rel family proteins. Mutational analysis demonstrates that the residues in this sequence that are identical in NFATp and Rel family proteins contribute to DNA binding by NFATp. Further, mutation of the threonine residue in this sequence to cysteine, as in Rel proteins, confers on NFATp a sensitivity to sulfhydryl modification similar to that of Rel family proteins. The results suggest that NFATp and Rel family proteins bind to DNA using similar structural motifs.

Highlights

From the Wana-Farber Cancer Institute, Department of Pathology, and lIDepartment of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115
One specific short sequence in NFATp (RAHYETEG), located near the NH2 terminus of the DNA-binding domain, resembles a highly conserved sequence (RFRYxCEG) that is located near the NH2 terminus of the ReI homology region and that has been implicated in DNA binding by ReI family proteins
NFATp, contained within the portion ofNFATp that is related to the ReI homology region, constitutes the minimal region required for specific binding to DNA and for interaction with Fos and Jun

Summary

A Similar DNA-binding Motif in NFAT Family Proteins and the ReI Homology Region*

(Received for publication, August 12, 1994, and in revised form, November 7, 1994). Jugnu Jaint§'Il, Emmanuel Burgeonts, Tina M. We show that a centrally located 187-amino-acid fragment of NFATp, contained within the portion ofNFATp that is related to the ReI homology region, constitutes the minimal region required for specific binding to DNA and for interaction with Fos and Jun. The amino terminus of this fragment contains a sequence similar to a highly conserved sequence motif at the amino terminus of the RHR, and the residues of this motif that are common to NFATp and the RHR contribute to DNA binding by NFATp as well as ReI family proteins.

EXPERIMENTAL PROCEDURES

N-terminal deletions

DISCUSSION

47 PYVKITEQPAGKALRFRYECEGRSAGSIPGVNS 79 dorsal til

10 N III III

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