Research in the Strieter lab seeks to understand how ubiquitin-dependent signaling directs proteasomal degradation and maintains protein homeostasis. A central focus of our work is defining how the nature of a ubiquitin modification—and the properties of the modified substrate—govern recognition, processing, and degradation by the proteasome.
How are ubiquitin modifications recognized and edited by the proteasome to regulate degradation?
A major focus of the laboratory is understanding how different ubiquitin modifications are interpreted by the proteasome and how these signals are actively remodeled during the degradation process. What features of ubiquitin chain architecture encode information for degradation? How do specific proteasomal subunits recognize these signals? And how does editing of ubiquitin modifications shape substrate fate?
Addressing these questions requires a detailed examination of the proteasome itself, with particular emphasis on the specificities and responses of individual proteasomal subunits to distinct ubiquitin architectures and modified substrates. Through this work, we aim to define the molecular logic by which the proteasome decodes ubiquitin signals to control protein fate.
Representative publication: Deol et al. Proteasome-Bound UCH37/UCHL5 Debranches Ubiquitin Chains to Promote Degradation. Mol. Cell 80 (2020): 796–809.
How can we define and decode the ubiquitin language?
Ubiquitin chains are structurally diverse, and a central question in the lab is how this diversity functions as a molecular language in ubiquitin-dependent signaling. What molecular features of ubiquitin modifications—linkage type, chain length, branching, and topology—are biologically meaningful?
To address this question, we develop integrative approaches that combine computational analysis with advanced top-down mass spectrometry to directly characterize complex ubiquitin architectures. This work is providing a detailed molecular description of ubiquitin modifications as they exist on substrates, enabling us to define the specific features of ubiquitin architecture that promote distinct ubiquitin-dependent signaling outcomes.
Representative publication: Shestoperova et al. Computationally Driven Top-Down Mass Spectrometry of Ubiquitinated Proteins. bioRxiv (2025). doi:10.1101/2025.07.24.666707.
How does the ubiquitin–proteasome system regulate the propagation of kinase signaling during learning and memory?
A major focus of this project is understanding how protein degradation contributes to the regulation of neuronal signaling pathways that underlie learning and memory. We study CaMKII, a highly abundant synaptic kinase that has long been regarded as a central mediator of synaptic plasticity and a molecular substrate of memory. Despite its importance, how the abundance and stability of CaMKII are regulated remains poorly understood.
Our work is motivated by the idea that regulated protein degradation is not simply a housekeeping process, but an active and essential mechanism for shaping the timing, persistence, and fidelity of signaling in neurons. Disruption of this regulation is increasingly linked to neurological and neurodevelopmental disorders, underscoring the importance of understanding how kinase stability and turnover contribute to brain function.