Pathomechanism of cell death induced by N-terminal fragment of profilaggrin

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09740
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: University of Toyama
• Principal Investigator: Makino Teruhiko 富山大学, 大学院医学薬学研究部(医学), 准教授 (90359711)
• Co-Investigator(Kenkyū-buntansha): 清水 忠道 富山大学, 大学院医学薬学研究部(医学), 教授 (70260396)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: profilaggrin / 表皮 / 角化 / 細胞死 / カルパイン

Outline of Final Research Achievements

Profilaggrin plays a critical role in keratinocyte terminal differentiation. During this process, a 55-kDa N-terminal fragment of profilaggrin (FLG-N) is translocated into the nucleus; thereafter, the cells became TUNEL-positive. We examined the molecular mechanism underlying the DNA degradation process induced by FLG-N in keratinocytes. Our findings suggest that calpine I and apoptosis-inducing factor may be associated with the FLG-N inducing-DNA degradation. We also found that FLG-N directly interacted with pinin, a transcriptional activator binding to the E-box 1 core sequence of the E-cadherin promoter gene, within the nucleus. Surprisingly, the suppression of pinin expression can induce cell death in keratinocytes even without interaction with FLG-N. In addition, 19 amino acids present in the N-terminal profilaggrin can induce cell death for squamous cell carcinoma (SCC) cell line HSC-1. We therefore hypothesized that FLG-N may be a novel therapeutic target in SCC.

Free Research Field

Keratinocyte biology