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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-26528

Tousseyn, T; Thathiah, A; Jorissen, E; Raemaekers, T; Konietzko, U; Reiss, K; Maes, E; Snellinx, A; Serneels, L; Nyabi, O; Annaert, W; Saftig, P; Hartmann, D; De Strooper, B (2009). ADAM10, the rate-limiting protease of regulated intramembrane proteolysis of Notch and other proteins, is processed by ADAMS-9, ADAMS-15, and the gamma-secretase. Journal of Biological Chemistry, 284(17):11738-11747.

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Abstract

ADAM10 is involved in the proteolytic processing and shedding of proteins such as the amyloid precursor protein (APP), cadherins, and the Notch receptors, thereby initiating the regulated intramembrane proteolysis (RIP) of these proteins. Here, we demonstrate that the sheddase ADAM10 is also subject to RIP. We identify ADAM9 and -15 as the proteases responsible for releasing the ADAM10 ectodomain, and Presenilin/gamma-Secretase as the protease responsible for the release of the ADAM10 intracellular domain (ICD). This domain then translocates to the nucleus and localizes to nuclear speckles, thought to be involved in gene regulation. Thus, ADAM10 performs a dual role in cells, as a metalloprotease when it is membrane-bound, and as a potential signaling protein once cleaved by ADAM9/15 and the gamma-Secretase.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Division of Psychiatric Research and Clinic for Psychogeriatric Medicine
DDC:610 Medicine & health
Language:English
Date:2009
Deposited On:06 Jan 2010 15:12
Last Modified:27 Nov 2013 18:48
Publisher:American Society for Biochemistry and Molecular Biology
ISSN:0021-9258
Additional Information:This research was originally published in Tousseyn, T; Thathiah, A; Jorissen, E; Raemaekers, T; Konietzko, U; Reiss, K; Maes, E; Snellinx, A; Serneels, L; Nyabi, O; Annaert, W; Saftig, P; Hartmann, D; De Strooper, B (2009). ADAM10, the rate-limiting protease of regulated intramembrane proteolysis of Notch and other proteins, is processed by ADAMS-9, ADAMS-15, and the gamma-secretase. Journal of Biological Chemistry, 284(17):11738-11747. © the American Society for Biochemistry and Molecular Biology.
Publisher DOI:10.1074/jbc.M805894200
PubMed ID:19213735

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