Integrins regulate adhesive cell-matrix interactions and mediate survival signals. On the other hand, unligated or free cytoplasmic fragments of integrins induce apoptosis in many cell types (integrin-mediated death). We have previously shown that b1 integrins expression protects keratinocyte stem cells from anoikis, while the role of the b1B integrin isoform has never been clarified. Here we report that suspended keratinocytes undergo apoptosis via the activation of caspase-8, independently of Fas/Fas Ligand system. Indeed, anti-b1 integrin neutralizing antibodies induced apoptosis in short-hairpin-RNA-Fas-Associated-Death-Domain treated cells. Moreover, before and during suspension, caspase-8 directly associated with b1 integrin, that in turn internalized and progressively degraded, shedding the cytoplasmic domain. b1B was expressed only in the cytoplasm in a perinuclear fashion and remained unaltered during suspension. At 24 hrs, as b1A located close to the nucleus, b1B co-localized with b1A and co-immunoprecipitated with caspase-8. Caspase-8 was activated earlier in b1B integrin transfected keratinocytes, and these cells underwent a higher rate of apoptosis than mock cells. By contrast, caspase-8 was not activated in siRNA b1B transfected cells. These results indicate that when b1A is unligated, b1B is responsible for “integrin-mediated death” in human keratinocytes.
|Data di pubblicazione:||2010|
|Titolo:||A previously unreported function of beta1B integrin isoform in caspase-8-dependent integrin-mediated keratinocyte death|
|Autore/i:||R. Lotti; A. Marconi; F. Truzzi; K. Dallaglio; C. Gemelli; R.G. Borroni; E. Palazzo; C. Pincelli|
|Digital Object Identifier (DOI):||10.1038/jid.2010.195|
|Codice identificativo ISI:||WOS:000282963600009|
|Codice identificativo Scopus:||2-s2.0-77957935569|
|Codice identificativo Pubmed:||20613771|
|Citazione:||A previously unreported function of beta1B integrin isoform in caspase-8-dependent integrin-mediated keratinocyte death / R. Lotti; A. Marconi; F. Truzzi; K. Dallaglio; C. Gemelli; R.G. Borroni; E. Palazzo; C. Pincelli. - In: JOURNAL OF INVESTIGATIVE DERMATOLOGY. - ISSN 0022-202X. - STAMPA. - 130(2010), pp. 2569-2577.|
|Tipologia||Articolo su rivista|
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