All Publications


  • Yca1 metacaspase: Diverse functions determine how yeast live and let die. FEMS yeast research Lam, D. K., Sherlock, G. 2023

    Abstract

    The Yca1 metacaspase was discovered due to its role in the regulation of apoptosis in Saccharomyces cerevisiae. However, the mechanisms that drive apoptosis in yeast remain poorly understood. Additionally, Yca1 and other metacaspase proteins have recently been recognized for their involvement in other cellular processes, including cellular proteostasis and cell cycle regulation. In this Minireview, we outline recent findings on Yca1 that will enable the further study of metacaspase multifunctionality and novel apoptosis pathways in yeast and other non-metazoans. In addition, we discuss advancements in high-throughput screening technologies that can be applied to answer complex questions surrounding the apoptotic and non-apoptotic functions of metacaspase proteins across a diverse range of species.

    View details for DOI 10.1093/femsyr/foad022

    View details for PubMedID 37002543

  • Exploring the "misfolding problem" by systematic discovery and analysis of functional-but-degraded proteins. Molecular biology of the cell Flagg, M. P., Lam, B., Lam, D. K., Le, T. M., Kao, A., Slaiwa, Y. I., Hampton, R. Y. 2023; 34 (13): ar125

    Abstract

    In both health and disease, the ubiquitin-proteasome system (UPS) degrades point mutants that retain partial function but have decreased stability compared with their wild-type counterparts. This class of UPS substrate includes routine translational errors and numerous human disease alleles, such as the most common cause of cystic fibrosis, ΔF508-CFTR. Yet, there is no systematic way to discover novel examples of these "minimally misfolded" substrates. To address that shortcoming, we designed a genetic screen to isolate functional-but-degraded point mutants, and we used the screen to study soluble, monomeric proteins with known structures. These simple parent proteins yielded diverse substrates, allowing us to investigate the structural features, cytotoxicity, and small-molecule regulation of minimal misfolding. Our screen can support numerous lines of inquiry, and it provides broad access to a class of poorly understood but biomedically critical quality-control substrates.

    View details for DOI 10.1091/mbc.E23-06-0248

    View details for PubMedID 37729018

    View details for PubMedCentralID PMC10848938