Regulation of T cell receptor signaling by protein acyltransferase DHHC21

Ying Fan, Bieerkehazhi Shayahati, Ritika Tewari, Darren Boehning, Askar M. Akimzhanov

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


S-acylation reversible—post-translational lipidation of cysteine residues—is emerging as an important regulatory mechanism in T cell signaling. Dynamic S-acylation is critical for protein recruitment into the T cell receptor complex and initiation of the subsequent signaling cascade. However, the enzymatic control of protein S-acylation in T cells remains poorly understood. Here, we report a previously uncharacterized role of DHHC21, a member of the mammalian family of DHHC protein acyltransferases, in regulation of the T cell receptor pathway. We found that loss of DHHC21 prevented S-acylation of key T cell signaling proteins, resulting in disruption of the early signaling events and suppressed expression of T cell activation markers. Furthermore, downregulation of DHHC21 prevented activation and differentiation of naïve T cells into effector subtypes. Together, our study provides the first direct evidence that DHHC protein acyltransferases can play an essential role in regulation of T cell-mediated immunity.

Original languageEnglish (US)
Pages (from-to)6471-6478
Number of pages8
JournalMolecular Biology Reports
Issue number8
StatePublished - Aug 1 2020

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics


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