Amino acid limitation regulates CHOP expression through a specific pathway independent of the unfolded protein response.
The gene encoding CHOP (C/EBP-homologous protein) is transcriptionally activated by many stimuli and by amino acid deprivation. CHOP induction was considered to be due to an accumulation of unfolded protein into the ER (unfolded protein response (UPR)). We investigate the role of the UPR in the induction of CHOP by amino acid deprivation and show that this induction is not correlated with BiP expression (an UPR marker). Moreover, amino acid deprivation and UPR inducers regulate the CHOP promoter activity using distinct cis elements. We conclude that amino acid deprivation does not activate the UPR and regulates CHOP expression through a pathway that is independent of the UPR.
Jousse
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UR 238 - Unité de Nutrition Cellulaire et Moléculaire, INRA de Theix, Saint Genès Champanelle, France.
Bruhat
A
A
Harding
H P
HP
Ferrara
M
M
Ron
D
D
Fafournoux
P
P
D000596:Amino Acids / Q000172:deficiency*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D015152:Blotting, Northern; D022762:CCAAT-Enhancer-Binding Proteins; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D013997:Time Factors; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000378:metabolism*; D014415:Tunicamycin / Q000494:pharmacology
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D022762:CCAAT-Enhancer-Binding Proteins; C497249:DDIT3 protein, human; D004268:DNA-Binding Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D014157:Transcription Factors; D014415:Tunicamycin; D051742:Transcription Factor CHOP; D007930:Leucine; D005947:Glucose