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Cell

Cell

IF: 45.5
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Lysine vitcylation is a vitamin C-derived protein modification that enhances STAT1-mediated immune response

Published:28 February 2025 DOI: 10.1016/j.cell.2025.01.043
Xiadi He, Qiwei Wang, Xin Cheng, Weihua Wang, Yutong Li, Yabing Nan, Jiang Wu, Bingqiu Xiu, Tao Jiang, Johann S. Bergholz, Hao Gu, Fuhui Chen, Guangjian Fan, Lianhui Sun, Shaozhen Xie, Junjie Zou, Sheng Lin, Yun Wei, James Lee, John M. Asara, Jean J. Zhao

Abstract

Vitamin C (vitC) is essential for health and shows promise in treating diseases like cancer, yet its mechanisms remain elusive. Here, we report that vitC directly modifies lysine residues to form “vitcyl-lysine”—a process termed vitcylation. Vitcylation occurs in a dose-, pH-, and sequence-dependent manner in both cell-free systems and living cells. Mechanistically, vitC vitcylates signal transducer and activator of transcription-1 (STAT1)- lysine-298 (K298), impairing its interaction with T?cell protein-tyrosine phosphatase (TCPTP) and preventing STAT1-Y701 dephosphorylation. This leads to enhanced STAT1-mediated interferon (IFN) signaling in tumor cells, increased major histocompatibility complex (MHC)/human leukocyte antigen (HLA) class I expression, and activation of anti-tumor immunity in?vitro and in?vivo. The discovery of vitcylation as a distinctive post-translational modification provides significant insights into vitC’s cellular function and therapeutic potential, opening avenues for understanding its biological effects and applications in disease treatment.

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Materials
Procduct Name CAS Molecular Formula Supplier Price
STAUROSPORINE 62996-74-1 C28H26N4O3 451 suppliers $10.00-$3200.00
STAUROSPORINE 62996-74-1 C28H26N4O3 451 suppliers $10.00-$3200.00
STAUROSPORINE 62996-74-1 C28H26N4O3 451 suppliers $10.00-$3200.00
STAUROSPORINE 62996-74-1 C28H26N4O3 451 suppliers $10.00-$3200.00
IOX2 931398-72-0 C19H16N2O5 150 suppliers $9.00-$1654.10
IOX2 931398-72-0 C19H16N2O5 150 suppliers $9.00-$1654.10
IOX2 931398-72-0 C19H16N2O5 150 suppliers $9.00-$1654.10
IOX2 931398-72-0 C19H16N2O5 150 suppliers $9.00-$1654.10
Bobcat339 (Bobcat 339) 2280037-51-4 C16H12ClN3O 52 suppliers Inquiry
Bobcat339 (Bobcat 339) 2280037-51-4 C16H12ClN3O 52 suppliers Inquiry

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