Intracellular and extracellular cytokine-like functions of prothymosin α: implications for the development of immunotherapies

Prothymosin alpha (ProT alpha) is a 12.5-kDa, highly acidic protein widely distributed in different cell types expressed intracellularly and extracellularly. ProT alpha does not contain a secretion-signal sequence and is released by a nonclassical secretory pathway with a cargo protein. New findings on the extracellular function of ProT alpha have yielded exciting insights into the cytokine-like functions of this host protein that stimulates type I interferon via Toll-like receptor 4. Here, we discuss the intracellular function of ProT alpha, how new findings of cytokine-like activities of ProT alpha aid our understanding of mechanisms that direct ProT alpha functions, and the potential application of these new insights to the development of immunotherapies.