| 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
|
| Resource |
| Mice |
RBRC09483 |
