Targeting N-Myristoylation Through NMT2 Prevents Cardiac Hypertrophy And Heart Failure

Overview

Journal JACC Basic Transl Sci

Date 2023 Dec 14

PMID 38094695

Authors

Yusuke Tomita

Fumiya Anzai

Tomofumi Misaka

Ryo Ogawara

Shohei Ichimura

Kento Wada

Yusuke Kimishima

Tetsuro Yokokawa

Takafumi Ishida

Yasuchika Takeishi

Affiliations

Soon will be listed here.

Abstract

Protein diversity can increase via N-myristoylation, adding myristic acid to an N-terminal glycine residue. In a murine model of pressure overload, knockdown of cardiac N-myristoyltransferase 2 (NMT2) by adeno-associated virus 9 exacerbated cardiac dysfunction, remodeling, and failure. Click chemistry-based quantitative chemical proteomics identified substrate proteins of N-myristoylation in cardiac myocytes. N-myristoylation of MARCKS regulated angiotensin II-induced cardiac pathological hypertrophy by preventing activations of Ca/calmodulin-dependent protein kinase II and histone deacetylase 4 and histone acetylation. Gene transfer of NMT2 to the heart reduced cardiac dysfunction and failure, suggesting targeting N-myristoylation through NMT2 could be a potential therapeutic approach for preventing cardiac remodeling and heart failure.

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