Activating transcription factor 1, commonly known as ATF1, is a protein involved in numerous cellular processes. It is a fundamental component within human cells, regulating gene expression and influencing various aspects of cell life. Its widespread importance is seen throughout the body.
Understanding ATF1’s Core Identity
ATF1 is a protein encoded by the ATF1 gene and is classified as a transcription factor, meaning it helps control the conversion of genetic information from DNA into RNA. It belongs to the basic leucine zipper (bZIP) family of proteins, characterized by a specific structural motif for DNA binding. This bZIP domain enables ATF1 to form dimers, either with itself or with other bZIP proteins.
Once these dimers form, ATF1 can bind to specific DNA sequences, such as the cAMP response element (CRE), found in many genes. By binding to these regions, ATF1 can either activate or repress the transcription of nearby genes. ATF1 is found in various cell types throughout the body, with notable prevalence in tissues like the liver. Its activity can be modified by post-translational changes, such as phosphorylation, which can enhance its ability to activate or repress gene expression.
ATF1’s Multifaceted Roles in Cells
ATF1 participates in several cellular processes. It contributes to the cell’s response to various forms of stress, including DNA damage and oxidative stress. In such situations, ATF1 can help cells adapt and survive by regulating genes involved in protective mechanisms.
Beyond stress responses, ATF1 is involved in regulating cell growth, differentiation, and cell survival. Its ability to control the expression of specific genes influences whether a cell divides, specializes into a particular cell type, or undergoes programmed cell death. For instance, its phosphorylation can enhance cell proliferation and transformation.
The Link Between ATF1 and Human Health
Dysregulation of ATF1 has been linked to several human health conditions, particularly various types of cancer. Alterations in ATF1’s function or expression can contribute to disease progression. One notable example is its role in melanoma, a severe form of skin cancer. In metastatic melanoma cells, ATF1, along with another transcription factor called CREB, is often found at elevated levels.
The overexpression of ATF1 and CREB can promote the metastatic potential of melanoma cells by influencing genes involved in invasion, such as those for metalloproteinase MMP-2 and the adhesion molecule MCAM/MUC18. These proteins also act as survival factors for melanoma cells, helping them resist cell death. Research has shown that disrupting ATF1 activity in melanoma cells can suppress tumor growth and metastatic spread in experimental models, and make cancer cells more susceptible to apoptosis.
ATF1 is also implicated in other cancers through specific genetic alterations. For instance, a fusion protein involving ATF1 and another gene, EWSR1, resulting from a chromosomal translocation, is associated with clear cell sarcoma, a rare cancer affecting soft tissue. This EWSR1-ATF1 fusion is also found in other rare neoplasms, including angiomatoid fibrous histiocytoma and certain salivary gland tumors. These fusion proteins can lead to dysregulated gene expression, contributing to the development of these malignancies.