RRC ID 80033
Author Fu Y, Li L, Zhang X, Deng Z, Wu Y, Chen W, Liu Y, He S, Wang J, Xie Y, Tu Z, Lyu Y, Wei Y, Wang S, Cui CP, Liu CH, Zhang L.
Title Systematic HOIP interactome profiling reveals critical roles of linear ubiquitination in tissue homeostasis.
Journal Nat Commun
Abstract Linear ubiquitination catalyzed by HOIL-1-interacting protein (HOIP), the key component of the linear ubiquitination assembly complex, plays fundamental roles in tissue homeostasis by executing domain-specific regulatory functions. However, a proteome-wide analysis of the domain-specific interactome of HOIP across tissues is lacking. Here, we present a comprehensive mass spectrometry-based interactome profiling of four HOIP domains in nine mouse tissues. The interaction dataset provides a high-quality HOIP interactome resource with an average of approximately 90 interactors for each bait per tissue. HOIP tissue interactome presents a systematic understanding of linear ubiquitination functions in each tissue and also shows associations of tissue functions to genetic diseases. HOIP domain interactome characterizes a set of previously undefined linear ubiquitinated substrates and elucidates the cross-talk among HOIP domains in physiological and pathological processes. Moreover, we show that linear ubiquitination of Integrin-linked protein kinase (ILK) decreases focal adhesion formation and promotes the detachment of Shigella flexneri-infected cells. Meanwhile, Hoip deficiency decreases the linear ubiquitination of Smad ubiquitination regulatory factor 1 (SMURF1) and enhances its E3 activity, finally causing a reduced bone mass phenotype in mice. Overall, our work expands the knowledge of HOIP-interacting proteins and provides a platform for further discovery of linear ubiquitination functions in tissue homeostasis.
Volume 15(1)
Pages 2974
Published 2024-4-6
DOI 10.1038/s41467-024-47289-2
PII 10.1038/s41467-024-47289-2
PMID 38582895
PMC PMC10998861
MeSH Animals Homeostasis Mice NF-kappa B / metabolism Ubiquitin* / metabolism Ubiquitin-Protein Ligases* / metabolism Ubiquitination
Mice RBRC09483