The Department of Chemical and Systems Biology Presents

Hening Lin, Ph.D.
Professor and HHMI Investigator
Department of Chemistry and Chemical Biology
Cornell University

Talk Title: “Protein acylation-deacylation cycles in cell signaling and disease”

Abstract: Protein post-translational modifications play important roles in cell signaling and stress response. My lab has been studying the regulatory roles of protein acylation, which was led by the sirtuins family of enzymes that are NAD+-dependent protein lysine deacylases. They were initially considered to be deacetylases, but we and others later found that many of them can remove other acyl groups, such as succinyl and long chain fatty acyl groups. Interestingly, SIRT2, a mammalian sirtuin that is mainly localized in the cytosol, is able to remove both acetyl and myristoyl/palmitoyl groups very efficiently. We discovered that the deacylation activity regulates several Ras super family of small GTPases. Through these studies, we found interesting examples that the acylation-deacylation cycle promotes cell signaling. Thus, inhibiting acylation and inhibiting deacylation actually produce the same biological effect. This cycle effect is different from the commonly known on-off switch effect of protein modifications and offers new opportunities to understand cell signaling and treat human diseases, including cancer and inflammation.

Reading Material:

1. Wang M, Lin H. Understanding the Function of Mammalian Sirtuins and Protein Lysine Acylation.
   Annu Rev Biochem. 2021 Jun 20;90:245-285. doi: 10.1146/annurev-biochem-082520-125411. Epub 2021 Apr 13. PMID: 33848425. 
2. Kosciuk T, Lin H, et al. NMT1 and NMT2 are lysine myristoyltransferases regulating the ARF6 GTPase cycle.
   Nat Commun. 2020 Feb 26;11(1):1067. doi: 10.1038/s41467-020-14893-x. PMID: 32103017; PMCID: PMC7044312.

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