QSOX1BIOFUNC

Frontiers of Oxidative Protein Folding and Assembly: Catalysis of Disulfide Formation Downstream of the Endoplasmic Reticulum

Coordinatore	WEIZMANN INSTITUTE OF SCIENCE    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Israel [IL]
Totale costo	1˙498˙083 €
EC contributo	1˙498˙083 €
Programma	FP7-IDEAS-ERC Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	ERC-2012-StG_20111109
Funding Scheme	ERC-SG
Anno di inizio	2012
Periodo (anno-mese-giorno)	2012-12-01   -   2017-11-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	WEIZMANN INSTITUTE OF SCIENCE  Organization address address: HERZL STREET 234 city: REHOVOT postcode: 7610001 contact info Titolo: Ms. Nome: Gabi Cognome: Bernstein Email: send email Telefono: +972 8 934 6728 Fax: +972 8 934 4165	IL (REHOVOT)	hostInstitution	1˙498˙083.00
2	WEIZMANN INSTITUTE OF SCIENCE  Organization address address: HERZL STREET 234 city: REHOVOT postcode: 7610001 contact info Titolo: Prof. Nome: Deborah Cognome: Fass Email: send email Telefono: +972 8 934 3214 Fax: +972 8 934 4136	IL (REHOVOT)	hostInstitution	1˙498˙083.00

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 Obiettivo del progetto (Objective)

'Quiescin sulfhydryl oxidase (QSOX), which catalyzes disulfide cross-linking in proteins, is up-regulated in many tumor types. QSOX is the only disulfide catalyst to undergo regulated secretion from cells, but the biological role of the enzyme, its substrates, and its mechanistic link to cancer are obscure. In addition to determining the first X-ray crystal structures of QSOXs, we recently discovered that QSOX is required for incorporation of laminins into basement membrane extracellular matrix (ECM). Fibroblasts depleted of QSOX make defective ECM that fails to support adherence and migration of tumor-derived cells in co-culture, but ECM composition and cell migration are restored by supplying recombinant QSOX exogenously. Our observations suggest a role for QSOX in building a microenvironment favorable for tumor cell survival and migration. We are motivated by a number of observations to expand our studies of QSOX enzymes. First, QSOX is ideally suited for single-molecule fluorescence resonance energy transfer experiments, which will shed light on hitherto invisible steps in the QSOX reaction cycle. Second, we have evidence for additional functions of QSOX with intriguing links to lipid metabolism and lipid storage diseases, and we are compelled to discover the pathways involved. Third, the modulation of tumor/stromal interactions is a promising direction for anti-metastatic cancer therapy, so the QSOX inhibitors we are developing may find use in the clinic as well as in the laboratory. Fourth, the complex QSOX expression patterns in developing and adult mammals prompted us to generate a conditional QSOX knockout mouse with which to explore QSOX function in vivo. In consolidating my laboratory, I will continue to rely heavily on my strengths as a structural biologist while pushing forward the frontier of our understanding of oxidative protein folding and assembly in cell and matrix biology, a fascinating subject that spans the Angstrom to the organism.'