English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

p18 is a key negative regulator of cell cycle progression and mediates cell cycle arrest at the G1/S phase. Ubiquitination is the prime mechanism in regulating p18 protein abundance. However, so far no post- translational regulator, especially DUBs, has been identified to regulate the protein stability of p18. In this paper, we identified CYLD as a deubiquitinase of p18, which binds to and removes the K48-linked polyubiquitylation chains conjugated onto p18, thus stabilizing the p18 protein. Loss of CYLD causes the degradation of p18 and induces the G1/S transition. Epstein–Barr virus (EBV), is the human oncovirus etiologically linked to nasopharyngeal carcinoma (NPC). Here we found that EBV drives a replication passive environment by deregulating the CYLD-p18 axis. Functionally, CYLD inhibits cell proliferation and tumorigenesis through p18 in vivo. Restoring CYLD prevents EBV induced viral replication and tumor growth. Collectively, our results identify CYLD directly stabilizes p18 to regulate the cellular G1/S transition. The reconstitution of CYLD-p18 axis could be a promising approach for EBV-positive cancer therapy.

Stabilization of p18 by deubiquitylase CYLD is pivotal for cell cycle progression and viral replication