DNp63a , a critical pro-proliferative factor and a marker of epidermal stemness, associates with the Y-box binding protein 1 (YB-1), a member of the cold shock protein family. YB-1 is an oncogenic, nucleic acid binding protein with pleiotropic function. Mainly localized in the cytoplasm, YB-1 is involved in alternative splicing, regulation of transcription and translation. Here we show that DNp63a induces the accumulation of post-translationally modified forms of YB-1 in the nucleus.Sumoylation and ubiquitination are both involved in this phenomenon. Silencing of YB-1 in differentiating HaCaT kertinocytes induces cell cycle arrest. YB-1 knockdown cells show early decline of cyclin D1, increase of p21WAF and reduced expression of the envelop precursor protein, involucrin. In proliferating HaCaT and squamous carcinoma cells, YB-1 triggers cell detachment and apoptosis suggesting that the functional interaction between DNp63a and YB-1 cooperate to support survival and proliferation of basal and transformed keratinocytes.

DNp63a and YB1-dependent regulation of keratinocyte adhesion and survival

DI MARTINO, ORSOLA;TROIANO, ANNAELENA;DI GIROLAMO, DANIELA;VIVO, MARIA;POLLICE, ALESSANDRA;LA MANTIA, GIROLAMA;CALABRO', VIOLA
2013

Abstract

DNp63a , a critical pro-proliferative factor and a marker of epidermal stemness, associates with the Y-box binding protein 1 (YB-1), a member of the cold shock protein family. YB-1 is an oncogenic, nucleic acid binding protein with pleiotropic function. Mainly localized in the cytoplasm, YB-1 is involved in alternative splicing, regulation of transcription and translation. Here we show that DNp63a induces the accumulation of post-translationally modified forms of YB-1 in the nucleus.Sumoylation and ubiquitination are both involved in this phenomenon. Silencing of YB-1 in differentiating HaCaT kertinocytes induces cell cycle arrest. YB-1 knockdown cells show early decline of cyclin D1, increase of p21WAF and reduced expression of the envelop precursor protein, involucrin. In proliferating HaCaT and squamous carcinoma cells, YB-1 triggers cell detachment and apoptosis suggesting that the functional interaction between DNp63a and YB-1 cooperate to support survival and proliferation of basal and transformed keratinocytes.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/592880
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