慢性淋巴细胞白血病
赖氨酸
乙酰化
癌症研究
白血病
车站3
医学
免疫学
化学
生物化学
信号转导
氨基酸
基因
作者
Uri Rozovski,David Harris,Ping Li,Zhiming Liu,Preetesh Jain,Alessandra Ferrajoli,Jan A. Burger,Philip A. Thompson,Nitin Jain,William G. Wierda,Michael J. Keating,Zeev Estrov
出处
期刊:Oncotarget
[Impact Journals, LLC]
日期:2018-09-14
卷期号:9 (72): 33710-33718
被引量:10
标识
DOI:10.18632/oncotarget.26110
摘要
Signal transducer and activator of transcription (STAT)-3 might be phosphorylated or acetylated. Unlike the phosphorylation of STAT3, little is known about the acetylation of STAT3 in chronic lymphocytic leukemia (CLL) cells. Because acetylation activates STAT3 transcription, we sought to study the acetylation status of STAT3 in CLL cells. Using Western immunoblotting, immunoprecipitation, and flow cytometry we found that, apart from its constitutive serine phosphorylation, STAT3 is constitutively acetylated on lysine 685 residues. Because the acetyltransferase p300 was found to acetylate STAT3 on lysine 685 residues, we wondered whether p300 acetylates STAT3 in CLL cells. Using Western immunoblotting we detected high levels of p300 protein in CLL but not normal B cells. Transfection of CLL cells with p300 small-interfering (si) RNA downregulated p300 transcripts as well as p300 and acetyl-STAT3 protein levels. In addition, p300 siRNA attenuated STAT3-DNA binding and downregulated mRNA levels of STAT3-regulated genes. Furthermore, transfection of CLL cells with p300-siRNA induced a 3-fold increase in the rate of spontaneous apoptosis. Taken together, our data suggest that in CLL cells STAT3 p300 induces constitutive acetylation and activation of STAT3. Whether inhibition of STAT3 acetylation might provide clinical benefit in patients with CLL remains to be determined.
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