Nuclear protein 1 induced by ATF4 in response to various stressors acts as a positive regulator on the transcriptional activation of ATF4.
Nuclear protein 1 (NUPR1) was originally identified as p8, a member of the family of HMG-I/Y transcription factors induced in response to various cellular stressors. However, the signaling pathway underlying NUPR1 induction by cellular stresses remains to be established. In this study, we found that the expression of NUPR1 by various stresses induced by activating transcription factor 4 (ATF4). Loss of ATF4 using siRNA significantly diminished NUPR1 expression. Overexpression of ATF4 caused NUPR1 levels to rise. NUPR1 expression was associated with enhanced transcriptional activation of genes of ATF4 downstream, suggesting that the protein promoted the transcription of stress-regulated genes via positive feedback on the ATF4 pathway.
Jin
Hyeon-Ok
HO
Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Nowon-gu, Seoul, Korea.
Seo
Sung-Keum
SK
Woo
Sang-Hyeok
SH
Choe
Tae-Boo
TB
Hong
Seok-Il
SI
Kim
Jong-Il
JI
Park
In-Chul
IC
D051701:Activating Transcription Factor 4 / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D025461:Feedback, Physiological; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D015854:Up-Regulation
D051701:Activating Transcription Factor 4; D051792:Basic Helix-Loop-Helix Proteins; D009363:Neoplasm Proteins; C491643:NUPR1 protein, human