| First Author | Liu H | Year | 2021 |
| Journal | EMBO Rep | Volume | 22 |
| Issue | 5 | Pages | e52063 |
| PubMed ID | 33769697 | Mgi Jnum | J:307060 |
| Mgi Id | MGI:6711927 | Doi | 10.15252/embr.202052063 |
| Citation | Liu H, et al. (2021) E3 ubiquitin ligase NEDD4L negatively regulates keratinocyte hyperplasia by promoting GP130 degradation. EMBO Rep 22(5):e52063 |
| abstractText | 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. |
