In the human body, proteins are the microscopic workhorses that perform a vast array of tasks necessary for life. They provide structure to cells, transport materials, and accelerate chemical reactions. One particular group of these molecules is the S100 family of proteins, which are activated by calcium. Within this family is a protein named S100A7, also known by the name psoriasin, a reference to its discovery in skin affected by psoriasis. The story of S100A7 reveals how a single type of protein can have multiple, sometimes contrasting, roles depending on its location and the surrounding cellular environment.
The S100A7 Protein: Gene, Structure, and Location
The blueprint for S100A7 is located in a specific region of our genetic material known as chromosome 1q21, a cluster that houses the instructions for at least 13 different S100 family members. Like other S100 proteins, it possesses specialized calcium-binding sections called EF-hand motifs. These structures act like a pair of hands that, upon binding to calcium ions, change the protein’s shape and activate its various functions.
Interestingly, S100A7 is somewhat unusual because one of its two EF-hand motifs does not bind calcium effectively. In addition to calcium, S100A7’s function can be influenced by zinc ions, which help stabilize the protein when it pairs up with another S100A7 molecule to form a functional unit called a homodimer.
The location of S100A7 within the body’s tissues and even inside individual cells can vary significantly. It is commonly found within the main compartment of the cell, the cytoplasm, or in the nucleus where the genetic material is stored. However, cells can also secrete S100A7 into the extracellular space, allowing it to travel and communicate with other cells. Its presence is most prominent in what are known as squamous epithelia, the layers of cells that form the surface of the skin and line certain organs and passages in the body.
Biological Functions of S100A7
The S100A7 protein is involved in several processes that govern the life of a cell. It plays a part in regulating the cell cycle, the orderly sequence of events through which a cell duplicates its contents and divides into two. The protein also contributes to cellular differentiation, the process by which a cell changes from one type to another, more specialized type.
One of the most notable functions of S100A7 is its activity as an antimicrobial peptide, forming a part of the body’s innate, or built-in, defense system. Research has shown it is particularly effective against certain types of bacteria, most famously Escherichia coli. When secreted onto the skin, S100A7 can directly kill these invading microbes, helping to prevent infections.
The protein’s defensive capabilities are linked to its ability to bind zinc ions. S100A7 can essentially starve bacteria of this necessary nutrient, a process sometimes referred to as “zinc piracy.” By sequestering the available zinc in its environment, S100A7 makes it difficult for bacteria to survive and multiply.
S100A7 in Immune System Activity
Beyond its direct action against microbes, S100A7 plays a broader role as a signaling molecule within the immune system. When cells are stressed or damaged, they can release S100A7 into their surroundings. In this context, the protein acts as an “alarmin,” a type of danger signal that alerts the immune system to a potential problem.
Once in the extracellular space, S100A7 can attract specific types of immune cells to the site of injury or infection. It has been shown to function as a chemotactic factor, a chemical that draws cells like neutrophils and a class of T-cells known as CD4+ T-cells toward it. These cells are key players in the inflammatory response. The protein achieves this by interacting with a receptor on the surface of these immune cells called the Receptor for Advanced Glycation End Products (RAGE), which then triggers internal signaling pathways that mediate the immune response.
This ability to recruit and activate immune cells makes S100A7 a contributor to inflammation. While inflammation is a normal and necessary part of fighting infection and repairing tissue, the activity of S100A7 can be a double-edged sword. In situations of chronic disease, this constant signaling can contribute to persistent inflammation that may cause more harm than good.
S100A7 and Human Diseases
In psoriatic skin, the expression of S100A7 is dramatically increased compared to healthy skin. This overexpression contributes to the inflammatory environment and the hyperproliferation, or excessive growth, of skin cells that characterize the disease.
The role of S100A7 in cancer is highly complex and appears to vary depending on the type of cancer. In some cases, such as in certain forms of breast, skin, and lung cancer, high levels of S100A7 are associated with more aggressive tumors and metastasis, the spread of cancer to other parts of the body. For example, it can promote the invasion of cancer cells by influencing the cell’s internal scaffolding and increasing the secretion of enzymes that break down surrounding tissue. Its interaction with proteins like RanBPM and Jab1/COP9 has been linked to these pro-cancer activities in breast cancer cells.
Conversely, in other contexts, S100A7’s effects are not as clear-cut and may even be linked to better outcomes. The presence of S100A7 in the urine of patients with bladder squamous cell carcinoma has led to investigations into its potential use as a biomarker for detecting or monitoring the disease.