The Unconventional Role of ABHD17A in Increasing the S-Palmitoylation and Antiviral Activity of IFITM1 by Downregulating ABHD16A

The Unconventional Role of ABHD17A in Increasing the S-Palmitoylation and Antiviral Activity of IFITM1 by Downregulating ABHD16A

The broad-spectrum antiviral functions of interferon-inducible transmembrane 1 (IFITM1) rely on S-palmitoylation post-translational modification. α/β-hydrolase domain-containing 17A (ABHD17A) has been reported to be responsible for protein depalmitoylation over the past decade, but whether and how A...

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Bibliographic Details
Main Authors: Xuemeng Shi, Shuaiwu Chen, Mingyang Liu, Yali Fan, Xin Wen, Jingyi Wang, Xiaoling Li, Huimin Liu, Lin Mao, Li Yu, Yuxin Hu, Jun Xu
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Biomolecules
Subjects:
ABHD17A
IFITM
S-palmitoylation
post-translational modification
virus infection
Online Access:https://www.mdpi.com/2218-273X/15/7/992
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Summary:The broad-spectrum antiviral functions of interferon-inducible transmembrane 1 (IFITM1) rely on S-palmitoylation post-translational modification. α/β-hydrolase domain-containing 17A (ABHD17A) has been reported to be responsible for protein depalmitoylation over the past decade, but whether and how ABHD17A regulates the dynamic S-palmitoylation modification of IFITM1 remains unknown. Here, we demonstrated that ABHD17A physically interacts with IFITM1 and increases the S-palmitoylation level of IFITM1. Sequence alignment revealed that ABHD17A lacked the DHHC motif, which is capable of catalyzing the S-palmitoylation modification. Thus, we screened multiple candidate palmitoylating and depalmitoylating enzymes that may contribute to ABHD17A-induced upregulation of IFITM1 S-palmitoylation. The recently discovered depalmitoylase ABHD16A was significantly downregulated by ABHD17A, which counteracted the palmitate-removing reactions of ABHD16A on IFITM1 and subsequently upregulated the S-palmitoylation level and antiviral activity of IFITM1. Our work therefore elucidated the unconventional role of depalmitoylase ABHD17A in elevating the S-palmitoylation modification, expanded the biological functions of ABHD17A in innate immunity, and provided potential targets for viral disease therapy.
ISSN:2218-273X

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