Alcohol induces RNA polymerase III-dependent transcription through c-Jun by co-regulating TATA-binding protein (TBP) and Brf1 expression
Authors: Hide Tsukamoto
Keigo Machida
Deborah L Johnson
Shuping Zhong
Journal: Journal of Biological Chemistry (2011)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Chronic alcohol consumption; steatohepatitis; cirrhosis; hepatocellular carcinoma; RNA polymerase III
Affiliations: Department of Biochemistry and Molecular Biology and the Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90033, USA. 

Abstract:  Chronic alcohol consumption is associated with steatohepatitis and cirrhosis, enhancing the risk for hepatocellular carcinoma. RNA polymerase (pol) III transcribes a variety of small, untranslated RNAs, including tRNAs and 5S rRNAs, which determine the biosynthetic capacity of cells. Increased RNA pol III-dependent transcription, observed in transformed cells and human tumors, is required for oncogenic transformation. Given that alcohol consumption increases risk for liver cancer, we examined whether alcohol regulates this class of genes. Ethanol induces RNA pol III-dependent transcription in both HepG2 cells and primary mouse hepatocytes in a manner that requires ethanol metabolism and the activation of JNK1. This regulatory event is mediated, at least in part, through the ability of ethanol to induce expression of the TFIIIB components, Brf1, and the TATA-binding protein (TBP). Induction of TBP, Brf1, and RNA pol III-dependent gene expression is driven by enhanced c-Jun expression. Ethanol promotes a marked increase in the direct recruitment of c-Jun to TBP, Brf1, and tRNA gene promoters. Chronic alcohol administration in mice leads to enhanced expression of TBP, Brf1, tRNA, and 5S rRNA gene transcription in the liver. These alcohol-dependent increases are more pronounced in transgenic animals that express the HCV NS5A protein that display increased incidence of liver tumors. Together, these results identify a new class of genes that are regulated by alcohol through the co-regulation of TFIIIB components and define a central role for c-Jun in this process. 

Retracted: No

PubPeer comments:
 ![file] , 
 Dear Sir Madam, Thank you for your mention about the image of figure 2A (Left panel) of our paper in JBC, 2011. I misused an image as JNK1 in the Fig.2A (Left panel). I am so sorry about the mistake. Fig.2 (left panel) indicated that the cellular levels of JNK1 and u03b2-actin didnu2019t display changes after alcohol treatment of the cells, while Fig.2A (right panel) and Fig.2C (left panel) of the paper also proved it. Here, JNK1 and u03b2-actin only stand for a loading control of protein usage. Sometimes, JNK1 and u03b2-actin revealed similar bands as their molecular weights were close. However, it was still a mistake. I am apology for that. Fortunately, the conclusion didnu2019t be affected as ethanol only increased the levels of phosphorylation JNK1 (p-JNK1), but didnu2019t alter non-phosphorylation JNK1 (JNK1). In future, we will carefully check a manuscript before submitting. We will try to do our best in the study of alcohol-associated cancer. I appreciate your help. Thank you very much! Sincerely, Shuping ,