p53‐dependent transcriptional regulation of EDA2R and its involvement in chemotherapy‐induced hair loss

Abstract

a b s t r a c tThe p53 tumor suppressor coordinates a multitude of cellular and organismal processes and exerts its activities mainly by activation of gene transcription. Here we describe the transcriptional activation of ectodysplasin A2 receptor (EDA2R) by p53 in a variety of cell types and tissues. We demonstrate that treatment of cancer cells with the ligand EDA-A2, known to specifically activate EDA2R, results in p53-dependent cell death. Moreover, we show that EDA2R is transactivated by p53 during chemotherapy-induced hair-loss, although its presence is not necessary for this process. These data shed new light on the role of EDA2R in exerting p53 function.

Laser Capture Microdissected Mucosa versus Whole Tissue Specimens for Assessment of Radiation-Induced Dynamic Molecular and Pathway Changes in the Small Intestine

“…EDA2R is a type III transmembrane protein of the TNFR (tumor necrosis factor receptor) superfamily and has been identified as a p53 target which regulates p53-mediated anoikis [31]–[33]. Eda2r negatively regulates focal adhesion kinase (FAK), a central component of focal adhesion.…”

Testing Chemotherapeutic Agents in the Feather Follicle Identifies a Selective Blockade of Cell Proliferation and a Key Role for Sonic Hedgehog Signaling in Chemotherapy-Induced Tissue Damage

“…A p53-dependent apoptosis program, which likely involves Fas-dependent signaling events, was suggested to underlie CIA (Botchkarev et al, 2000;Sharov et al, 2004). Other molecules such as ectodysplasin A receptor, epidermal growth factor receptor, and the eukaryotic initiation factor 4E have also been implicated (Brosh et al, 2010;Bichsel et al, 2013;Nasr et al, 2013;Paik et al, 2013).…”

Rap2b, a novel p53 target, regulates p53-mediated pro-survival function

“…[32][33][34][35][36][37][38] Btg2, Mdm2 and Cdkn1a are known cell cycle arrest genes, while Eda2r, Bbc3 and Tnfrsf10b are apoptotic genes. [32][33][34][35][36][37][38] Alox5 is involved in p53-mediated senescence through regulating the production of reactive oxygen species. 39 Adrb2 is a p53 target in response to ultraviolet (UV) irradiation in melanocytes, but its function is unknown.…”