Cyclic AMP-dependent transcription factor ATF-1
Function
This protein binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. Binds to the Tax-responsive element (TRE) of HTLV-I. Mediates PKA-induced stimulation of CRE-reporter genes. Represses the expression of FTH1 and other antioxidant detoxification genes. Triggers cell proliferation and transformation.
Involvement in disease
Angiomatoid fibrous histiocytoma
AFH
A distinct variant of malignant fibrous histiocytoma that typically occurs in children and adolescents and is manifest by nodular subcutaneous growth. Characteristic microscopic features include lobulated sheets of histiocyte-like cells intimately associated with areas of hemorrhage and cystic pseudovascular spaces, as well as a striking cuffing of inflammatory cells, mimicking a lymph node metastasis.
None
The gene represented in this entry may be involved in disease pathogenesis. Chromosomal aberrations involving ATF1 are found in patients with angiomatoid fibrous histiocytoma. Translocation t(12;16)(q13;p11.2) with FUS generates a chimeric ATF1/FUS protein. Translocation t(12;22)(q13;q12) with EWSR1 generates a chimeric ATF1/EWSR1 protein.
Post-translational modifications
Phosphorylated at Ser-198 by HIPK2 in response to genotoxic stress. This phosphorylation promotes transcription repression of FTH1 and other antioxidant detoxification genes. The CDK3-mediated phosphorylation at Ser-63 promotes its transactivation and transcriptional activities. Phosphorylated at Ser-63 by RPS6KA4 and RPS6KA5 in response to mitogenic or stress stimuli.
Sequence Similarities
Belongs to the bZIP family. ATF subfamily.
Cellular localization
- Nucleus
Alternative names
Cyclic AMP-dependent transcription factor ATF-1, cAMP-dependent transcription factor ATF-1, Activating transcription factor 1, Protein TREB36, ATF1