IMMUNOLOGY2026™ Conference Recordings For Attendees-Site-Selective Proximity-Synthetic Editors Rewrite p53 Acetylation to Dynamically Control Treg Lineage Differentiation

Site-Selective Proximity-Synthetic Editors Rewrite p53 Acetylation to Dynamically Control Treg Lineage Differentiation

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Video Summary

The speaker presented a new class of small molecules called “site-selective proximity synthetic editors” designed to control T cell fate by rewriting specific acetylation sites on p53. He explained that p53 plays a non-canonical role in regulating regulatory T cells (Tregs), and that acetylation at lysine 120 promotes Foxp3 expression and Treg differentiation, while P300-linked acetylation favors effector T cells. Using computational, cellular, and genetic approaches, the team showed that disrupting K120 acetylation reduces Treg formation. They then developed heterobifunctional molecules that bring either TIP60 or P300 into proximity with p53 to selectively induce distinct acetylation patterns. TIP60 editors increased Tregs in vitro and improved outcomes in mouse transplant and autoimmune models, prolonging graft survival and ameliorating EAE, while P300 editors had the opposite effect. The work suggests a new therapeutic strategy for precisely tuning immune responses.

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Date April 16, 2026 12:45 PM - 1:00 PM

Room 253

Session Therapeutic Modulation of T Cells for Autoimmune Diseases

Speaker Francisco Gonzalez

Track Therapeutic Approaches to Autoimmunity (THER)

Year 2026

Keywords

site-selective proximity synthetic editors

p53 acetylation

regulatory T cells

TIP60 P300 heterobifunctional molecules

immune response modulation

April 16, 2026 12:45 PM - 1:00 PM

253

Therapeutic Modulation of T Cells for Autoimmune Diseases

Francisco Gonzalez

Therapeutic Approaches to Autoimmunity (THER)

2026