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The USP12/46 deubiquitinases protect integrins from ESCRT-mediated lysosomal degradation

ABSTRACT: The functions of integrins are tightly regulated via multiple mechanisms including trafficking and degradation. Integrins are repeatedly internalized, routed into the endosomal system and either degraded by the lysosome or recycled back to the plasma membrane. The ubiquitin system dictates whether internalized proteins are degraded or recycled. Here, we used a genetic screen and proximity-dependent biotin identification to identify deubiquitinase(s) that control integrin surface levels. We found that a ternary deubiquitinating complex, comprised of USP12 (or the homologous USP46), WDR48 and WDR20, stabilizes β1 integrin (Itgb1) by preventing ESCRT-mediated lysosomal degradation. Mechanistically, the USP12/46-WDR48-WDR20 complex removes ubiquitin from the cytoplasmic tail of internalized Itgb1 in early endosomes, which in turn prevents ESCRT-mediated sorting and Itgb1 degradation.

INSTRUMENT(S): timsTOF Pro, Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Barbara Steigenberger

LAB HEAD: Reinhard Fässler

PROVIDER: PXD054760 | Pride | 2024-09-06

REPOSITORIES: pride

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			Action	DRS
	20220218_coreQEP2_BaSt_LC12-19_SA_Orbi4128_Sample01.raw	Raw
	20220218_coreQEP2_BaSt_LC12-19_SA_Orbi4130_Sample01.raw	Raw
	20220218_coreQEP2_BaSt_LC12-19_SA_Orbi4130_Sample02.raw	Raw
	20220218_coreQEP2_BaSt_LC12-19_SA_Orbi4130_Sample03.raw	Raw
	20220218_coreQEP2_BaSt_LC12-19_SA_Orbi4130_Sample04.raw	Raw

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