NucMAPP, a novel approach for studying nuclear degradation

Subcellular compartments and organelles offers precise spatial control to maintain homeostasis. One principle site is the nucleus where tight regulation of chromatin dynamics takes place to ensure that proper transcriptional responses are elicited in response to different environmental cues or stress. While it is known that proteasomes are localized to the nucleus to support degradation of specific proteins, our understanding of the underlying mechanisms remain poorly understood. Here we describe the development of a new approach, NucMAPP, which enables the capturing of naturally-cleaved proteasomal peptides from nuclei under various physiological and pathological conditions. We show differential degradation of specific substrates by perturbing nuclear transport or nuclear proteostasis and offer new insight into the nuclear degradome.