UVB radiation represses CYLD expression in melanocytes

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 factorκB 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.

Schneider, NadjaFriedrich-Alexander University Erlangen-Nürnberg (author)
Massoumi, RaminLund University,Lunds universitet,Molekylär tumörpatologi,Forskargrupper vid Lunds universitet,Molecular Tumor Pathology,Lund University Research Groups(Swepub:lu)expp-rma (author)
Hellerbrand, ClausFriedrich-Alexander University Erlangen-Nürnberg (author)
Bosserhoff, Anja KatrinFriedrich-Alexander University Erlangen-Nürnberg (author)
Friedrich-Alexander University Erlangen-NürnbergMolekylär tumörpatologi (creator_code:org_t)

By the author/editor: Kuphal, Silke; Schneider, Nadja; Massoumi, Ramin; Hellerbrand, Cla ...; Bosserhoff, Anja ...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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