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Title: Chemical Biology Approaches for Investigating the Functions of Lysine Acetyltransferases
Abstract

The side‐chain acetylation of lysine residues in histones and non‐histone proteins catalyzed by lysine acetyltransferases (KATs) represents a widespread posttranslational modification (PTM) in the eukaryotic cells. Lysine acetylation plays regulatory roles in major cellular pathways inside and outside the nucleus. In particular, KAT‐mediated histone acetylation has an effect on all DNA‐templated epigenetic processes. Aberrant expression and activation of KATs are commonly observed in human diseases, especially cancer. In recent years, the study of KAT functions in biology and disease has greatly benefited from chemical biology tools and strategies. In this Review, we present the past and current accomplishments in the design of chemical biology approaches for the interrogation of KAT activity and function. These methods and probes are classified according to their mechanisms of action and respective applications, with both strengths and limitations discussed.

 
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NSF-PAR ID:
10048717
Author(s) / Creator(s):
 ;  ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Angewandte Chemie International Edition
Volume:
57
Issue:
5
ISSN:
1433-7851
Page Range / eLocation ID:
p. 1162-1184
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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  2. Abstract

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    Basic Protocol 1: Labeling HAT protein substrates with azide/alkyne‐biotin

    Alternate Protocol: Labeling protein substrates of HATs with azide/alkyne‐TAMRA for in‐gel visualization

    Support Protocol 1: Expression and purification of HAT mutants

    Support Protocol 2: Synthesis of Ac‐CoA surrogates

    Basic Protocol 2: Streptavidin enrichment of biotinylated HAT substrates

    Basic Protocol 3: Chemoproteomic identification of HAT substrates

    Basic Protocol 4: Validation of specific HAT substrates with western blotting

     
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