The Expanding Landscape of Moonlighting Proteins in Yeasts

Abstract

Moonlighting proteins are multifunctional proteins that participate in unrelated biological processes and that are not the result of gene fusion. A certain number of these proteins have been characterized in yeasts, and the easy genetic manipulation of these microorganisms has been useful for a thorough analysis of some cases of moonlighting. As the awareness of the moonlighting phenomenon has increased, a growing number of these proteins are being uncovered. In this review, we present a crop of newly identified moonlighting proteins from yeasts and discuss the experimental evidence that qualifies them to be classified as such. The variety of moonlighting functions encompassed by the proteins considered extends from control of transcription to DNA repair or binding to plasminogen. We also discuss several questions pertaining to the moonlighting condition in general. The cases presented show that yeasts are important organisms to be used as tools to understand different aspects of moonlighting proteins.

FIG 1

Scheme for autoregulation of Pdc1 synthesis. (A) In S. cerevisiae, a hypothetical protein, Era, together with an activating protein A (Pdc2?), activates the transcription of PDC1. The Pdc1 protein in the cytosol would sequester the activating protein and decrease PDC1 transcription (50). (B) In K. lactis, transcription of KlPDC1 is activated by the regulatory protein Rag3, an ortholog of Pdc2. When the concentration of Pdc1 is high, most of the Rag3 protein is bound to it and trapped in the cytosol; consequently, the rate of KlPDC1 transcription is low. When Pdc1 levels decrease, Rag3 is liberated and can enter the nucleus, activating KlPDC1 transcription (52).