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Article: MT1-MMP cleaves Dll1 to negatively regulate Notch signalling to maintain normal B-cell development

TitleMT1-MMP cleaves Dll1 to negatively regulate Notch signalling to maintain normal B-cell development
Authors
KeywordsB-cell differentiation
Dll1
MT1-MMP
Notch signalling
Issue Date2011
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/emboj/index.html
Citation
Embo Journal, 2011, v. 30 n. 11, p. 2281-2293 How to Cite?
AbstractNotch signalling controls the differentiation of haematopoietic progenitor cells (HPCs). Here, we show that loss of membrane-type 1 matrix metalloproteinase (MT1-MMP, MMP14), a cell surface protease expressed in bone marrow stromal cells (BMSCs), increases Notch signalling in HPCs and specifically impairs B-lymphocyte development. When co-cultured with BMSCs in vitro, HPCs differentiation towards B lymphocytes is significantly compromised on MT1-MMP-deficient BMSCs and this defect could be completely rescued by DAPT, a specific Notch signalling inhibitor. The defective B-lymphocyte development could also be largely rescued by DAPT in vivo. MT1-MMP interacts with Notch ligand Delta-like 1 (Dll1) and promotes its cleavage on cell surface in BMSCs. Ectopic MT1-MMP cleaves Dll1 and results in diminished Notch signalling in co-cultured cells. In addition, recombinant MT1-MMP cleaves a synthetic Dll1 peptide at the same site where MT1-MMP cleaves Dll1 on the cell surface. Our data suggest that MT1-MMP directly cleaves Dll1 on BMSCs to negatively regulate Notch signalling to specifically maintain normal B-cell development in bone marrow. © 2011 European Molecular Biology Organization.
Persistent Identifierhttp://hdl.handle.net/10722/138967
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 5.489
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Research Grant Council of Hong KongHKU7513/03M
G_HK027/06
HKU781808M
HKU3/07C
CRCG fund201007176204
National Science Foundation of China
Ministry of Science and Technology of CHINA2007CB50740
2011CB964700
UGC
Deutsche ForschungsgemeinschaftSFB 829
Funding Information:

We thank Maggie Chow for proofreading of the manuscript, S Artavanis-Tsakonas (Harvard Medical School) for human Notch1 cDNA and YY Lui for technical assistance in flow cytometry. This work was supported by Research Grant Council of Hong Kong (HKU7513/03M, G_HK027/06, HKU781808M, HKU3/07C), the CRCG fund (201007176204), the National Science Foundation of China (Hong Kong/Macau Young Scholar Scheme), and grants from Ministry of Science and Technology of CHINA (973 Projects 2007CB50740, 2011CB964700), the UGC AoE Program for 'Developmental Genomics and Skeletal Research' and Deutsche Forschungsgemeinschaft through SFB 829 (to CM). Emma Campbell, Freelance Medical Editor, UK, provided editing assistance.

References
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DC FieldValueLanguage
dc.contributor.authorJin, Gen_HK
dc.contributor.authorZhang, Fen_HK
dc.contributor.authorChan, KMen_HK
dc.contributor.authorXavier Wong, HLen_HK
dc.contributor.authorLiu, Ben_HK
dc.contributor.authorCheah, KSEen_HK
dc.contributor.authorLiu, Xen_HK
dc.contributor.authorMauch, Cen_HK
dc.contributor.authorLiu, Den_HK
dc.contributor.authorZhou, Zen_HK
dc.date.accessioned2011-09-23T05:43:19Z-
dc.date.available2011-09-23T05:43:19Z-
dc.date.issued2011en_HK
dc.identifier.citationEmbo Journal, 2011, v. 30 n. 11, p. 2281-2293en_HK
dc.identifier.issn0261-4189en_HK
dc.identifier.urihttp://hdl.handle.net/10722/138967-
dc.description.abstractNotch signalling controls the differentiation of haematopoietic progenitor cells (HPCs). Here, we show that loss of membrane-type 1 matrix metalloproteinase (MT1-MMP, MMP14), a cell surface protease expressed in bone marrow stromal cells (BMSCs), increases Notch signalling in HPCs and specifically impairs B-lymphocyte development. When co-cultured with BMSCs in vitro, HPCs differentiation towards B lymphocytes is significantly compromised on MT1-MMP-deficient BMSCs and this defect could be completely rescued by DAPT, a specific Notch signalling inhibitor. The defective B-lymphocyte development could also be largely rescued by DAPT in vivo. MT1-MMP interacts with Notch ligand Delta-like 1 (Dll1) and promotes its cleavage on cell surface in BMSCs. Ectopic MT1-MMP cleaves Dll1 and results in diminished Notch signalling in co-cultured cells. In addition, recombinant MT1-MMP cleaves a synthetic Dll1 peptide at the same site where MT1-MMP cleaves Dll1 on the cell surface. Our data suggest that MT1-MMP directly cleaves Dll1 on BMSCs to negatively regulate Notch signalling to specifically maintain normal B-cell development in bone marrow. © 2011 European Molecular Biology Organization.en_HK
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/emboj/index.htmlen_HK
dc.relation.ispartofEMBO Journalen_HK
dc.subjectB-cell differentiationen_HK
dc.subjectDll1en_HK
dc.subjectMT1-MMPen_HK
dc.subjectNotch signallingen_HK
dc.subject.meshB-Lymphocytes - physiology-
dc.subject.meshCell Differentiation-
dc.subject.meshIntercellular Signaling Peptides and Proteins - metabolism-
dc.subject.meshMatrix Metalloproteinase 14 - deficiency - metabolism-
dc.subject.meshReceptors, Notch - metabolism-
dc.titleMT1-MMP cleaves Dll1 to negatively regulate Notch signalling to maintain normal B-cell developmenten_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0261-4189&volume=30&issue=11&spage=2281&epage=2293&date=2011&atitle=MT1-MMP+cleaves+Dll1+to+negatively+regulate+Notch+signalling+to+maintain+normal+B-cell+development-
dc.identifier.emailChan, KM: ming616@graduate.hku.hken_HK
dc.identifier.emailLiu, B: ppliew@hku.hken_HK
dc.identifier.emailCheah, KSE: hrmbdkc@hku.hken_HK
dc.identifier.emailZhou, Z: zhongjun@hkucc.hku.hken_HK
dc.identifier.authorityChan, KM=rp01757en_HK
dc.identifier.authorityLiu, B=rp01485en_HK
dc.identifier.authorityCheah, KSE=rp00342en_HK
dc.identifier.authorityZhou, Z=rp00503en_HK
dc.description.naturepostprint-
dc.identifier.doi10.1038/emboj.2011.136en_HK
dc.identifier.pmid21572390-
dc.identifier.pmcidPMC3117651-
dc.identifier.scopuseid_2-s2.0-79957924074en_HK
dc.identifier.hkuros194495en_US
dc.identifier.hkuros190285-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79957924074&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume30en_HK
dc.identifier.issue11en_HK
dc.identifier.spage2281en_HK
dc.identifier.epage2293en_HK
dc.identifier.eissn1460-2075-
dc.identifier.isiWOS:000292424700018-
dc.publisher.placeUnited Kingdomen_HK
dc.relation.projectRole of MT1-MMP in wound healing and tumorigenesis-
dc.identifier.scopusauthoridJin, G=55224723000en_HK
dc.identifier.scopusauthoridZhang, F=36116166900en_HK
dc.identifier.scopusauthoridChan, KM=8631854500en_HK
dc.identifier.scopusauthoridXavier Wong, HL=37125424800en_HK
dc.identifier.scopusauthoridLiu, B=7408693394en_HK
dc.identifier.scopusauthoridCheah, KSE=35387746200en_HK
dc.identifier.scopusauthoridLiu, X=47461459300en_HK
dc.identifier.scopusauthoridMauch, C=7005219019en_HK
dc.identifier.scopusauthoridLiu, D=21934191400en_HK
dc.identifier.scopusauthoridZhou, Z=8631856300en_HK
dc.identifier.citeulike9315553-
dc.identifier.issnl0261-4189-

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