Acetylation of TIP60 at K104 is essential for metabolic stress-induced apoptosis in cells of hepatocellular cancer.

Exp Cell Res

Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, United States; Beijing Proteome Research Center, Beijing 102200, China.

Published: January 2018

Tumor cells often encounter hypoglycemic microenvironment due to rapid cell expansion. It remains elusive how tumors reprogram the genome to survive the metabolic stress. The tumor suppressor TIP60 functions as the catalytic subunit of the human NuA4 histone acetyltransferase (HAT) multi-subunit complex and is involved in many different cellular processes including DNA damage response, cell growth and apoptosis. Attenuation of TIP60 expression has been detected in various tumor types. The function of TIP60 in tumor development has not been fully understood. Here we found that suppressing TIP60 inhibited p53 K120 acetylation and thus rescued apoptosis induced by glucose deprivation in hepatocellular cancer cells. Excitingly, Lys-104 (K104), a previously identified lysine acetylation site of TIP60 with unknown function, was observed to be indispensable for inducing p53-mediated apoptosis under low glucose condition. Mutation of Lys-104 to Arg (K104R) impeded the binding of TIP60 to human NuA4 complex, suppressed the acetyltransferase activity of TIP60, and inhibited the expression of pro-apoptotic genes including NOXA and PUMA upon glucose starvation. These findings demonstrate the critical regulation of TIP60/p53 pathway in apoptosis upon metabolic stress and provide a novel insight into the down-regulation of TIP60 in tumor cells.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360337PMC
http://dx.doi.org/10.1016/j.yexcr.2017.11.028DOI Listing

Publication Analysis

Top Keywords

hepatocellular cancer
8
tumor cells
8
metabolic stress
8
tip60
8
human nua4
8
tip60 tumor
8
tip60 inhibited
8
apoptosis
5
tumor
5
acetylation tip60
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!