UVB radiation represses CYLD expression in melanocytes
- Silke Kuphal
- Nadja Schneider
- Ramin Massoumi
- Claus Hellerbrand
- Anja Katrin Bosserhoff
Published online on: October 3, 2017
Copyright: © Kuphal et al.
This is an open access article distributed under the terms of Creative Commons Attribution License.
CYLD lysine 63 deubiquitinase (CYLD) was originally identified as a tumor suppressor that is mutated in familial cylindromatosis. Unlike in cylindromatosis, downregulation of the deubiquitinase CYLD in melanoma, a highly aggressive tumor, is not caused by mutations in the CYLD gene, but rather by a constitutive and high expression of the snail family transcriptional repressor 1 (SNAIL1). A reduced CYLD level leads to B‑cell lymphoma‑3/p50/p52‑dependent nuclear factor‑κB activation, which in turn triggers the expression of genes such as cyclin D1 and N‑cadherin. Elevated levels of cyclin D1 and N‑cadherin promote melanoma proliferation and invasion. By analyzing the regulation of CYLD expression in melanocytes, the present study identified a signaling pathway that is regulated in response to ultraviolet B (UVB) radiation in melanocytes. UVB light leads to an extracellular signal‑regulated kinase‑mediated induction of SNAIL1 and subsequent downregulation of CYLD expression in normal human epithelial melanocytes. The UVB‑mediated suppression of CYLD in melanocytes may have a key role in the reaction to UV stimuli, and may also potentially be involved in the early malignant transformation processes.