A Bifunctional Intronic Element Regulates the Expression of the Arginine/Lysine Transporter Cat-1 via Mechanisms Involving the Purine-rich Element Binding Protein A (Pur alpha)

作者：Huang Charlie C; Chiribau Calin Bogdan; Majumder Mithu; Chiang Cheng Ming; Wek Ronald C; Kelm Robert J Jr; Khalili Kamel; Snider Martin D; Hatzoglou Maria^*

来源：Journal of Biological Chemistry, 2009, 284(47): 32312-32320.

DOI：10.1074/jbc.M109.024471

Expression of the arginine/lysine transporter Cat-1 is highly induced in proliferating and stressed cells via mechanisms that include transcriptional activation. A bifunctional INE (intronic element) within the first intron of the Cat-1 gene was identified and characterized in this study. The INE had high sequence homology to an amino acid response element and was shown to act as a transcriptional enhancer in unstressed cells by binding the transcription factor, purine-rich element binding protein A (Pur alpha). During endoplasmic reticulum stress, binding of Pur alpha to the INE decreased; the element acted as a positive regulator in early stress by binding of the transcription factor ATF4 and as a negative regulator in prolonged stress by binding the stress-induced C/EBP family member, CHOP. We conclude that transcriptional control of the Cat-1 gene is tightly controlled by multiple cis-DNA elements, contributing to regulation of cationic amino acid transport for cell growth and proliferation. In addition, we propose that genes may use stress-response elements such as the INE to support basal expression in the absence of stress.

• 出版日期2009-11-20