Related Experiment Video
Updated: Nov 11, 2025

Detection of Protein Ubiquitination
Published on: August 19, 2009
E3 ubiquitin ligase NEDD4L negatively regulates keratinocyte hyperplasia by promoting GP130 degradation
Huan Liu1, Wenlong Lin1, Zhiyong Liu1
1Institute of Immunology and Bone Marrow Transplantation Center, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
Abstract:
Psoriasis is mainly characterized by abnormal hyperplasia of keratinocytes and immune cells infiltrating into the dermis and epidermis. Neural precursor cell expressed developmentally downregulated 4-like (NEDD4L) is a highly conserved HECT type E3 ligase that plays an important role in regulating physiological and pathological processes. Here, we identify NEDD4L as a negative regulator of psoriasis. Nedd4l significantly inhibits imiquimod (IMQ)-induced skin hyperplasia, and this effect is attributed to the inhibitory effect of NEDD4L on IL-6/GP130 signaling in keratinocytes. Mechanistically, NEDD4L directly interacts with GP130 and mediates its Lys-27-linked ubiquitination and proteasomal degradation. Moreover, the expression of NEDD4L is downregulated in the epidermis from IMQ-treated mice and psoriasis patients and negatively correlates with the protein levels of GP130 and p-STAT3 in clinical samples. Collectively, we uncover an inhibitory role of NEDD4L in the pathogenesis of psoriasis and suggest a new therapeutic strategy for the treatment of psoriasis.
More Related Videos
11:32Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
10:51Isolation and Culture of Primary Mouse Keratinocytes from Neonatal and Adult Mouse Skin
Published on: July 14, 2017
Related Concept Videos
Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
Regulated Protein Degradation
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Abnormal Proliferation
Negative Regulator Molecules
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
PI3K/mTOR/AKT Signaling Pathway