Nutrient sensing-the key to fungal p53-like transcription factors?

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The mammalian tumour suppressor protein, p53, plays an important role in cell cycle control, DNA repair and apoptotic cell death. Transcription factors belonging to the “p53-like” superfamily are found exclusively in the Amorphea branch of eukaryotes, which includes animals, fungi and slime molds. Many members of the p53-like superfamily (proteins containing p53, Rel/Dorsal, T-box, STAT, Runt, Ndt80, and the CSL DNA-binding domains) are involved in development. Two families of p53-like proteins (Ndt80 and CSL) are widespread in fungi as well as animals. The Basidiomycetes and the Ascomycetes have undergone reciprocal loss of the Ndt80 and CSL classes of transcription factors, with the CSL class preserved in only one branch of Ascomycetes and the Ndt80 class found in only one branch of Basidiomycetes. Recent studies have greatly expanded the known functions of fungal Ndt80-like proteins and shown that they play important roles in sexual reproduction, cell death, N-acetylglucosamine sensing and catabolism, secondary metabolism, and production of extracellular hydrolases such as proteases, chitinases and cellulases. In the opportunistic pathogen, Candida albicans, Ndt80-like proteins are essential for hyphal growth and virulence and also play a role in antifungal resistance. These recent studies have confirmed that nutrient sensing is a common feature of fungal Ndt80-like proteins and is also found in fungal CSL-like transcription factors, which in animals is the mediator of Notch signalling. Thus, nutrient sensing may represent the ancestral role of the p53-like superfamily.