Differential Effects of Histone Acetyltransferase GCN5 or PCAF Knockdown on Urothelial Carcinoma Cells

Koutsogiannouli, Evangelia A.; Wagner, Nicholas; Hader, Christiane; Pinkerneil, Maria; Hoffmann, Michèle J.; Schulz, Wolfgang A.

doi:10.3390/ijms18071449

Cited by 20 publications

(13 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6 , B and C ), suggesting that the acetylation of Lys-90 by GCN5 has a biological function different from that of Lys-31 by PCAF, which is involved in the defense responses of the host. Similar opposing effects of acetylation by PCAF and GCN5 were reported in tumor cells ( 33 , 34 ). Acetylation on different lysine residues in the tumor repressor p53 caused a tumor-promoting role of GCN5 and a tumor-repressing role of PCAF ( 33 ).…”

Section: Discussionsupporting

confidence: 77%

Influenza A virus nucleoprotein is acetylated by histone acetyltransferases PCAF and GCN5

Hatakeyama

Shoji

Yamayoshi

et al. 2018

Journal of Biological Chemistry

View full text Add to dashboard Cite

Histone acetylation plays crucial roles in transcriptional regulation and chromatin organization. Viral RNA of the influenza virus interacts with its nucleoprotein (NP), whose function corresponds to that of eukaryotic histones. NP regulates viral replication and has been shown to undergo acetylation by the cAMP-response element (CRE)–binding protein (CBP) from the host. However, whether NP is the target of other host acetyltransferases is unknown. Here, we show that influenza virus NP undergoes acetylation by the two host acetyltransferases GCN5 and P300/CBP-associated factor (PCAF) and that this modification affects viral polymerase activities. Western blot analysis with anti–acetyl-lysine antibody on cultured A549 human lung adenocarcinoma epithelial cells infected with different influenza virus strains indicated acetylation of the viral NP. A series of biochemical analyses disclosed that the host lysine acetyltransferases GCN5 and PCAF acetylate NP in vitro. MS experiments identified three lysine residues as acetylation targets in the host cells and suggested that Lys-31 and Lys-90 are acetylated by PCAF and GCN5, respectively. RNAi-mediated silencing of GCN5 and PCAF did not change acetylation levels of NP. However, interestingly, viral polymerase activities were increased by the PCAF silencing and were decreased by the GCN5 silencing, suggesting that acetylation of the Lys-31 and Lys-90 residues has opposing effects on viral replication. Our findings suggest that epigenetic control of NP via acetylation by host acetyltransferases contributes to regulation of polymerase activity in the influenza A virus.

show abstract

Section: Discussionsupporting

confidence: 77%

Influenza A virus nucleoprotein is acetylated by histone acetyltransferases PCAF and GCN5

Hatakeyama

Shoji

Yamayoshi

et al. 2018

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…A series of bladder cancer cell lines, representing different stages and grades of the disease, were used as described previously ( Koutsogiannouli et al, 2017 ). Most of the functional experiments were conducted using the moderately differentiated cell line BFTC905, which was established from a grade 2 stage C urothelial carcinoma ( Cheng et al, 1995 ).…”

Section: Methodsmentioning

confidence: 99%

Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer

et al. 2018

Self Cite

View full text Add to dashboard Cite

Olfactory receptors (ORs) are a large group of G-protein coupled receptors predominantly found in the olfactory epithelium. Many ORs are, however, ectopically expressed in other tissues and involved in several diseases including cancer. In this study, we describe that one OR, OR10H1, is predominantly expressed in the human urinary bladder with a notably higher expression at mRNA and protein level in bladder cancer tissues. Interestingly, also significantly higher amounts of OR10H1 transcripts were detectable in the urine of bladder cancer patients than in the urine of control persons. We identified the sandalwood-related compound Sandranol as a specific agonist of OR10H1. This deorphanization allowed the functional characterization of OR10H1 in BFTC905 bladder cancer cells. The effect of receptor activation was morphologically apparent in cell rounding, accompanied by changes in the cytoskeleton detected by β-actin, T-cadherin and β-Catenin staining. In addition, Sandranol treatment significantly diminished cell viability, cell proliferation and migration and induced a limited degree of apoptosis. Cell cycle analysis revealed an increased G1 fraction. In a concentration-dependent manner, Sandranol application elevated cAMP levels, which was reduced by inhibition of adenylyl cyclase, and elicited intracellular Ca2+ concentration increase. Furthermore, activation of OR10H1 enhanced secretion of ATP and serotonin. Our results suggest OR10H1 as a potential biomarker and therapeutic target for bladder cancer.

show abstract

“…PCAF is an important member of the GCN5-related N-terminal acetyltransferase family, which has histone acetyltransferase activity and plays an important role in regulating various cellular physiological activities including cell growth, differentiation, apoptosis, and so on [30,31]. Jia et al found that PCAF is downregulated in hepatocellular carcinoma (HCC) tissues, and overexpression of PCAF in HCC cells can promote autophagy and cause tumor cell death [9].…”

Section: Discussionmentioning

confidence: 99%

Downregulation of P300/CBP-Associated Factor Attenuates Myocardial Ischemia-Reperfusion Injury Via Inhibiting Autophagy

Qiu¹,

Xu²,

Xia³

et al. 2020

Int. J. Med. Sci.

View full text Add to dashboard Cite

Cardiomyocyte autophagy plays an important role in myocardial ischemia-reperfusion injury (MIRI). P300/CBP-associated factor (PCAF) was involved in the regulation of autophagy. However, the role of PCAF in MIRI is currently unknown. This study was to investigate whether downregulation of PCAF attenuate MIRI. The results showed that the expression of PCAF was significantly increased in MIRI in vivo and in vitro. Downregulation of PCAF not only inhibited autophagy and damage of H9c2 cells induced by hypoxia-reoxygenation, but also reduced autophagy and myocardial infarct size during myocardial ischemia-reperfusion in rats. In addition, downregulation of PCAF promoted activation of PI3K/Akt/mTOR signaling pathway in cardiomyocytes during hypoxia-reoxygenation. Wortmannin, a PI3K/Akt inhibitor, could abrogate the effects of downregulation of PCAF on cardiomyocytes autophagy. These results demonstrated that downregulation of PCAF alleviated MIRI by inhibiting cardiomyocyte autophagy through PI3K/Akt/mTOR signaling pathway. Thus, PCAF may be a potential target for prevention and treatment of MIRI.

show abstract

Differential Effects of Histone Acetyltransferase GCN5 or PCAF Knockdown on Urothelial Carcinoma Cells

Cited by 20 publications

References 35 publications

Influenza A virus nucleoprotein is acetylated by histone acetyltransferases PCAF and GCN5

Influenza A virus nucleoprotein is acetylated by histone acetyltransferases PCAF and GCN5

Characterization of the Olfactory Receptor OR10H1 in Human Urinary Bladder Cancer

Downregulation of P300/CBP-Associated Factor Attenuates Myocardial Ischemia-Reperfusion Injury Via Inhibiting Autophagy

Contact Info

Product

Resources

About