Suppressin, also known as DEAF1 is a transcription factor required for embryonic development. Suppressin contains one SAND domain and one SLCterminal MYND-type zinc finger. It interacts with LMO4 and CLIM-2, suggesting that it plays a role mediating cell fate and embryonic pattern formation. Suppressin is expressed in a variety of tissues and localizes to the nucleus. Several isoforms exist due to alternative splicing and, depending on the isoform, Suppressin is secreted in some cell types. Secreted Suppressin can function to inhibit cell proliferation, arresting cells in the G0 or G1 phase. Mutations in the gene encoding Suppressin may result in a growth advantage leading to the development and progression of neoplasia. This suggest that Supressin is a potential target for cancer therapy.
Function: Transcription factor that binds to sequence with multiple copies of 5'-TTC[CG]G-3' present in its own promoter and that of the HNRPA2B1 gene. Down-regulates transcription of these genes. Binds to the retinoic acid response element (RARE) 5'-AGGGTTCACCGAAAGTTCA-3'. Activates the proenkephalin gene independently of promoter binding, probably through protein-protein interaction. When secreted, behaves as an inhibitor of cell proliferation, by arresting cells in the G0 or G1 phase. Required for neural tube closure and skeletal patterning. Regulates epithelial cell proliferation and side-branching in the mammary gland. Controls the expression of peripheral tissue antigens in pancreatic lymph nodes. Isoform 1 displays greater transcriptional activity than isoform 4. Isoform 4 may inhibit transcriptional activity of isoform 1 by interacting with isoform 1 and retaining it in the cytoplasm.
Subunit: Homodimer (Probable). Isoform 1 and isoform 4 may form a heterodimer. Binds to LMO4 (via its SLCterminus), LMO2 and CLIM2. May interact with the corepressor NCOR.
Subcellular Location: Isoform 1: Nucleus. Cytoplasm. Note=Cytoplasmic in non-mucinous colorectal carcinoma. When expressed alone, localized almost exclusively in the nucleus but, when expressed with isoform 4, nuclear expression decreases to 32% and cytoplasmic expression increases by 270%. Isoform 2: Secreted. Note=Secreted in some cell types. Isoform 3: Secreted. Note=Secreted in some cell types. Isoform 4: Cytoplasm. Nucleus. Note=When expressed alone, localizes mainly in the cytoplasm but, when expressed with isoform 1, nuclear localization is enhanced.
Tissue Specificity: Expressed in various tissues and cells such as in peripheral mononuclear cells and hormone-secreting pituitary cells. Expression in pancreatic lymph nodes of patients with type 1 diabetes is 20 times higher than in healthy controls.
