Dataset Information

Large-scale proteome and ubiquitination landscape of patients with OTULIN haploinsufficiency Part1 of 3

ABSTRACT: The molecular basis of interindividual clinical variability upon infection with Staphylococcus aureus is unclear. We describe patients with haploinsufficiency for the linear deubiquitinase OTULIN, encoded on chromosome 5p. The patients suffer from episodes of life-threatening necrosis, typically triggered by S. aureus infections. The disorder is phenocopied in patients with the 5p- (Cri-du-Chat) chromosomal deletion syndrome. OTULIN haploinsufficiency causes an accumulation of linear ubiquitin in dermal fibroblasts, but TNF-receptor NF-κB-signaling remains intact. Blood leukocyte subsets are unaffected. The OTULIN-dependent accumulation of caveolin-1 in dermal fibroblasts — but not leukocytes — facilitates the cytotoxic damage inflicted by the staphylococcal virulence factor α-toxin. Naturally elicited antibodies to α-toxin contribute to incomplete clinical penetrance. By disrupting cell-intrinsic immunity to α-toxin in non-leukocytic cells, human OTULIN haploinsufficiency underlies life-threatening staphylococcal disease.

INSTRUMENT(S): Orbitrap Fusion Lumos, timsTOF Pro, Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Soren Heissel

LAB HEAD: Jean-Laurent Casanova

PROVIDER: PXD032727 | Pride | 2022-06-13

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	MS206264LUM_Andras_Casanova_OTULIN_PRM_Run1_F1.raw	Raw
	MS206264LUM_Andras_Casanova_OTULIN_PRM_Run1_F14.raw	Raw
	MS206264LUM_Andras_Casanova_OTULIN_PRM_Run1_F5.raw	Raw
	MS206264LUM_Andras_Casanova_OTULIN_PRM_Run1_F6.raw	Raw
	MS206264LUM_Andras_Casanova_OTULIN_PRM_Run1_F7.raw	Raw

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Publications

Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal α-toxin.

Spaan András N AN Neehus Anna-Lena AL Laplantine Emmanuel E Staels Frederik F Ogishi Masato M Seeleuthner Yoann Y Rapaport Franck F Lacey Keenan A KA Van Nieuwenhove Erika E Chrabieh Maya M Hum David D Migaud Mélanie M Izmiryan Araksya A Lorenzo Lazaro L Kochetkov Tatiana T Heesterbeek Dani A C DAC Bardoel Bart W BW DuMont Ashley L AL Dobbs Kerry K Chardonnet Solenne S Heissel Søren S Baslan Timour T Zhang Peng P Yang Rui R Bogunovic Dusan D Wunderink Herman F HF Haas Pieter-Jan A PA Molina Henrik H Van Buggenhout Griet G Lyonnet Stanislas S Notarangelo Luigi D LD Seppänen Mikko R J MRJ Weil Robert R Seminario Gisela G Gomez-Tello Héctor H Wouters Carine C Mesdaghi Mehrnaz M Shahrooei Mohammad M Bossuyt Xavier X Sag Erdal E Topaloglu Rezan R Ozen Seza S Leavis Helen L HL van Eijk Maarten M J MMJ Bezrodnik Liliana L Blancas Galicia Lizbeth L Hovnanian Alain A Nassif Aude A Bader-Meunier Brigitte B Neven Bénédicte B Meyts Isabelle I Schrijvers Rik R Puel Anne A Bustamante Jacinta J Aksentijevich Ivona I Kastner Daniel L DL Torres Victor J VJ Humblet-Baron Stéphanie S Liston Adrian A Abel Laurent L Boisson Bertrand B Casanova Jean-Laurent JL

Science (New York, N.Y.) 20220617 6599

The molecular basis of interindividual clinical variability upon infection with <i>Staphylococcus aureus</i> is unclear. We describe patients with haploinsufficiency for the linear deubiquitinase OTULIN, encoded by a gene on chromosome 5p. Patients suffer from episodes of life-threatening necrosis, typically triggered by <i>S. aureus</i> infection. The disorder is phenocopied in patients with the 5p- (Cri-du-Chat) chromosomal deletion syndrome. OTULIN haploinsufficiency causes an accumulation of ...[more]

PMID: 35587511

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