A murine ATFa-associated factor with transcriptional repressing activity.
The ATFa proteins, which are members of the CREB/ATF family of transcription factors, have previously been shown to interact with the adenovirus E1a oncoprotein and to mediate its transcriptional activity; they heterodimerize with Jun, Fos or related transcription factors, possibly altering their DNA-binding specificity; they also stably bind JNK2, a stress-induced protein kinase. Here we report the identification and characterization of a novel protein isolated in a yeast two-hybrid screen using the N-terminal half of ATFa as a bait. This 1306-residue protein (mAM, for mouse ATFa-associated Modulator) is rather acidic (pHi 4.5) and contains high proportions of Ser/Thr (21%) and Pro (11%) residues. It colocalizes and interacts with ATFa in mammalian cells, contains a bipartite nuclear localization signal and possesses an ATPase activity. Transfection experiments show that mAM is able to downregulate transcriptional activity, in an ATPase-independent manner. Our results indicate that mAM interacts with several components of the basal transcription machinery (TFIIE and TFIIH), including RNAPII itself. Together, these findings suggest that mAM may be involved in the fine-tuning of ATFa-regulated gene expression, by interfering with the assembly or stability of specific preinitiation transcription complexes.
De Graeve
F
F
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch, Communauté Urbaine de Strasbourg, France.
Bahr
A
A
Chatton
B
B
Kedinger
C
C
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary; D005314:Embryonic and Fetal Development; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D012319:RNA Polymerase II / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D019473:Transcription Factors, TFII; D014158:Transcription, Genetic
C408904:Atf7ip protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D018076:DNA, Complementary; D012097:Repressor Proteins; D014157:Transcription Factors; D019473:Transcription Factors, TFII; C066644:transcription factor TFIIE; D051758:Transcription Factor TFIIH; D012319:RNA Polymerase II; D000251:Adenosine Triphosphatases