{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T17:35:26Z","timestamp":1760204126385},"reference-count":72,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,12,7]],"date-time":"2005-12-07T00:00:00Z","timestamp":1133913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:p><jats:bold>Abstract:\u2002<\/jats:bold> Ultraviolet B (UVB) induces both apoptosis and skin cancer. We found that human keratinocytes (KC) immortalized by Human Papillomavirus (HPV)16 E6\/E7 were sensitized to UVB\u2010induced apoptosis, possibly representing a transient regression\u2010prone precancerous stage equivalent to actinic keratosis. To further examine which caspases are apical and essential, we utilized retroviral constructs expressing dominant\u2010negative caspase\u20109 (caspase\u20109\u2010DN) or Fas\u2010associated protein with death domain (FADD)\u2010DN as well as caspase inhibitor peptides. Caspase\u20109\u2010DN and zLEHD\u2010fmk both suppressed caspase\u20109, \u20103, and \u20108 activity after UVB exposure, as well as proteolytic processing of procaspase\u20103 into its active form, DNA fragmentation factor 45 cleavage, and internucleosomal DNA fragmentation. By contrast, stable expression of FADD\u2010DN in HPV\u2010immortalized KC did not inhibit UVB\u2010induced activation of caspases\u20109, \u20103, and \u20108 nor downstream apoptotic events, although inhibition of caspase\u20108 with zIETD\u2010fmk attenuated apoptosis. This study indicates that caspase\u20109 activation is upstream of caspases\u20103 and \u20108 and that UVB\u2010induced apoptosis in HPV\u2010immortalized human KC is death receptor (DR) independent and requires both caspase\u20109 upstream and caspase\u20108 downstream for maximal apoptosis. These studies further indicate that cell type as well as transformation state determine the sensitivity and mode of cell death (DR vs. mitochondrial apoptotic pathways) in response to UVB and explain the high regression rates of premalignant lesions.<\/jats:p>","DOI":"10.1111\/j.0906-6705.2005.00384.x","type":"journal-article","created":{"date-parts":[[2005,12,7]],"date-time":"2005-12-07T11:19:03Z","timestamp":1133954343000},"page":"23-34","source":"Crossref","is-referenced-by-count":16,"title":["Apoptosis induced by ultraviolet B in HPV\u2010immortalized human keratinocytes requires caspase\u20109 and is death receptor independent"],"prefix":"10.1111","volume":"15","author":[{"given":"Ahmad","family":"Daher","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia M.","family":"Simbulan\u2010Rosenthal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dean 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