Exploring the Protein Degradation Pathways: An Interview with Dr. Hongyong Fu

Within the cell, proteins serve not only as the structural foundation of life, but also as the essential machinery that powers virtually all biological functions. Their synthesis, modification, trafficking, and degradation are intricately coordinated processes that influence gene expression, signal transduction, and responses to the environment. For decades, Dr. Hongyong Fu has dedicated his research to unraveling the molecular mechanisms underlying protein degradation, with a particular focus on the ubiquitin/26S proteasome system (UPS) in eukaryotes. His work has centered around three major themes: the molecular architecture of the 26S proteasome, the biochemical and functional characterization of ubiquitin receptors, and the evolutionary and functional analysis of the OTU family of deubiquitinases (DUBs). These contributions have significantly deepened our understanding of UPS dynamics in plants and laid important groundwork for future applications in crop improvement and gene regulation.

Yet, Dr. Fu’s impact extends far beyond the laboratory and academic publications. As a long-serving Deputy Director of the Institute of Plant and Microbial Biology (IPMB), he has led great efforts to improve research infrastructure and daily working conditions. From upgrading growth chambers and reinforcing structural safety, to landscaping the institute’s grounds and refurbishing aging building walls, Dr. Fu has played a pivotal role in shaping a better and safer environment for all. He often says, “It makes me happy to do something useful for the institute,” which is modest in tone, but it reflects a deep and sincere commitment to both people and place.

In this interview, we revisit highlights from Dr. Fu’s scientific journey through four key publications that helped map the molecular mechanism of the UPS in plants. We also take a closer look at the improvements he has brought to IPMB that have shaped the daily experience of everyone who works and studies at the institute.

Early in his research career, Dr. Fu had a deep interest in the mechanisms of protein degradation. In a seminal paper published in The EMBO Journal in 2001, his team systematically mapped the subunit interactions within the regulatory particle (RP) of the yeast 26S proteasome using a yeast two-hybrid (Y2H) approach. The study then extended to Arabidopsis, where they compared homologous subunits in the COP9 signalosome (CSN)—a multi-subunit complex structurally related to the proteasome lid. Remarkably, they discovered a high degree of structural correspondence between the two complexes, supporting the hypothesis that both evolved from a common ancestral complex. More than just highlighting their evolutionary connection, this work also identified key interaction clusters that were later validated as secondary modules (subcomplexes) within the proteasome and signalosome. The findings laid a foundational framework for understanding how the 26S proteasome assembles and regulates substrate degradation, and provided early structural insights into the modular organization of its lid subcomplex.

📖 Original article:
Subunit interaction maps for the regulatory particle of the 26S proteasome and the COP9 signalosome
https://www.embopress.org/doi/full/10.1093/emboj/20.24.7096

Extending their investigation into proteasome function, Dr. Fu’s research team broadened their perspective in this study, published in The FEBS Journal in 2010, by taking a comparative approach to the critical step of ubiquitinated substrate recognition within the protein degradation system. Focusing on the major ubiquitin receptors in humans, yeast, and Arabidopsis, the team conducted biochemical interaction assays and site-directed mutagenesis analyses. While the primary receptors are conserved across species at the evolutionary level, the study revealed clear interspecies differences in the mechanisms and structural details of both direct receptors (RPN10 and RPN13) and indirect shuttle factors (RAD23, DSK2, and DDI1). These findings suggest that plants have evolved a uniquely integrated strategy for substrate recognition, reflecting a distinct logic of functional division. This cross-species comparative analysis not only sheds light on the evolutionary trajectory of the plant UPS but also provides valuable leads for future biochemical and structural investigations.

📖 Original article:
Cross-species divergence of the major recognition pathways of ubiquitylated substrates for ubiquitin/26S proteasome-mediated proteolysis
https://febs.onlinelibrary.wiley.com/doi/10.1111/j.1742-4658.2009.07531.x

Among the earliest ubiquitin receptors identified, RPN10 has long been considered essential for substrate recognition in the proteasome. However, in this study published in The Plant Cell, Dr. Fu and his team challenged this conventional understanding. They discovered that although the rpn10-2 Arabidopsis mutant exhibits severe developmental defects, these phenotypes could be fully rescued by a mutant form of RPN10 that is incapable of binding ubiquitin or the shuttle factor RAD23. Biochemical analyses revealed that the root of the problem was not a failure in substrate recognition, but rather instability in the assembly of the proteasome itself. This study fundamentally redefined the role of RPN10, which is not as a primary receptor for ubiquitinated substrates, but as a structural stabilizer crucial for proteasome assembly. The findings also suggest that substrate recognition in plants relies on a highly redundant network of ubiquitin receptors, rather than a single essential pathway.

📖 Original article:
The defective proteasome but not substrate recognition function is responsible for the null phenotypes of the Arabidopsis proteasome subunit RPN10
https://academic.oup.com/plcell/article/23/7/2754/6097204?login=true

In addition to his work on ubiquitin receptors, Dr. Fu has also focused on characterizing deubiquitylation enzymes (DUBs) in plants, particularly those belonging to the OTU (ovarian tumor-related) family. In a study published in Frontiers in Plant Science, his team conducted a comprehensive analysis of 12 OTU genes in Arabidopsis. Through phylogenetic comparisons and biochemical assays, they evaluated the substrate preferences of 11 OTU proteins with intact catalytic domains, revealing that each enzyme displayed specificity toward distinct ubiquitin linkages—such as K48, K63, or M1 chains. The findings suggest that different OTU members may be responsible for regulating distinct cellular processes, and that several of them appear to be plant-specific, potentially reflecting roles unique to plant biology. This study represents the first systematic exploration of the OTU DUB family in Arabidopsis, laying the groundwork for future investigations into how these enzymes contribute to plant development, signaling, and gene regulation. Building on this work, Dr. Fu’s group later analyzed mutants of one particular member, OTU5, and found that it modulates flowering time by influencing the transcription of major flowering repressors through histone methylation. This functional link between OTU5 and epigenetic regulation was further detailed in their 2023 publication in the International Journal of Molecular Sciences (Radjacommare et al., Int J Mol Sci 24(7):6176).

📖 Original article:
Distinct phylogenetic relationships and biochemical properties of Arabidopsis ovarian tumor-related deubiquitinases support their functional differentiation
https://www.frontiersin.org/journals/plant-science/articles/10.3389/fpls.2014.00084/full

Crafting a Better Environment for Science

Beyond his long-standing dedication to research and teaching, Dr. Fu has also served multiple terms as IPMB deputy director, bringing the same care and commitment to his administrative responsibilities. He modestly remarks, “I’m just happy to be able to contribute to the institute,” but those who work with him know he didn’t just get things done, he made sure they were done well. Under his leadership, the transformation of our basement plant growth chambers—from concept to completion—allowed for much more stable conditions for plant cultivation and experimental work. When the exterior tiles on the north wing began to deteriorate from years of wear, Dr. Fu coordinated their replacement, addressing safety concerns while also refreshing the building’s appearance.

Dr. Fu’s attention extended beyond infrastructure to the overall comfort of the institute’s spaces. As a member of the landscaping committee, he thoughtfully planned the arrangement of plants and revitalized multiple areas, bringing order and vitality to often-ignored corners. In recent years, he helped guide structural reinforcements, exterior wall restoration, and improvements to our outdoor landscape, and those efforts made our workplace safer, more functional, and more welcoming. One especially memorable act was his decision to transplant a Callery pear from Kinmen about four or five years ago, planting it at the front of the Agricultural Technology Building. It was just a small seedling at the time, but today it stands nearly two stories tall. When Dr. Fu mentioned it, he spoke of it casually, but the pride in his eyes told a different story.

Dr. Fu brings the same sincerity to his care for the research environment as he does to his scientific work. During his years as Deputy Director, IPMB has not only become safer and more comfortable, it has also become warmer and more like a home. He reminds us that the progress of a research institute isn’t measured only by publications or equipment, but also by the thoughtfulness and dedication embedded in the everyday details.

Whether dissecting the molecular intricacies of protein degradation or improving the physical corners of our institute, Dr. Fu has always moved forward with steady, thoughtful steps. His research has deepened our understanding of protein regulation in plants, while his administrative work has made our workplace more stable and welcoming. He may never call these accomplishments remarkable, but for those of us who know IPMB well, the traces he has left behind, in both science and space, speak volumes. We’re grateful for this opportunity to reflect on Dr. Fu’s many contributions, and we look forward to seeing how his work and presence continue to inspire, in new ways and new places.