Nuclear protein 1 induced by ATF4 in response to various stressors acts as a positive regulator on the transcriptional activation of ATF4

IUBMB Life. 2009 Dec;61(12):1153-8. doi: 10.1002/iub.271.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 4 / metabolism*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cell Line, Tumor
  • Feedback, Physiological
  • Gene Expression Regulation, Neoplastic*
  • HeLa Cells
  • Humans
  • Lung Neoplasms / metabolism
  • Models, Biological
  • Neoplasm Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Transcription, Genetic
  • Transcriptional Activation*
  • Up-Regulation

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • NUPR1 protein, human
  • Neoplasm Proteins
  • Activating Transcription Factor 4