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Yeast Signaling01:28

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Yeasts are single-celled organisms, but unlike bacteria, they are eukaryotes (cells with a nucleus). Cell signaling in yeast is similar to signaling in other eukaryotic cells. A ligand, such as a protein or a small molecule released from a yeast cell, attaches to a receptor on the cell surface. The binding stimulates second-messenger kinases to activate or inactivate transcription factors that further regulate gene expression. Many of the yeast intracellular signaling cascades have similar...
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Development of Chemical Tools for the Human YEATS Domain.

Xuejiao Shirley Guo1, Abdalrahman Khalifa1, Karthik Selvam2

  • 1Texas A&M Drug Discovery Center and Department of Chemistry, Texas A&M University, College Station, Texas 77843, United States.

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The YEATS domain reads histone acylation, impacting gene regulation and cancer. New chemical modulators offer targeted epigenetic therapies for malignancies.

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Area of Science:

  • Epigenetics
  • Molecular Biology
  • Cancer Biology

Background:

  • The YEATS domain is an evolutionarily conserved epigenetic reader.
  • It recognizes post-translational lysine acylation on histone tails.
  • YEATS domain proteins (ENL, AF9, YEATS2, GAS41) are linked to various cancers.

Purpose of the Study:

  • To review the structural basis of YEATS domain recognition of acyllysine modifications.
  • To discuss the disease-related consequences of aberrant YEATS activity.
  • To highlight recent advances in developing chemical modulators targeting YEATS domains.

Main Methods:

  • Structural analysis of YEATS domain-acyllysine interactions.
  • Review of literature on YEATS proteins in cancer pathogenesis.
  • Survey of emerging chemical modulators (peptide inhibitors, small molecules, PROTACs).

Main Results:

  • YEATS domains bind diverse acyllysine marks on histones.
  • Dysregulated YEATS activity contributes to malignancy.
  • Novel chemical modulators show promise for selective YEATS targeting.

Conclusions:

  • YEATS domain recognition mechanisms are key to understanding its epigenetic role.
  • Targeting YEATS domains offers a promising therapeutic strategy.
  • YEATS-directed therapies are advancing epigenetic drug discovery.