Genotoxic and endoplasmic reticulum stresses differentially regulate TRB3 expression.
TRB3 has recently been identified as a potential pro-apoptotic protein that may modulate the Akt/PKB-dependent signaling pathway. Here we report that TRB3 expression is strongly upregulated by endoplasmic reticulum (ER) stress-inducing agents that (1) promote ER Ca2+ pool depletion or (2) disrupt protein trafficking. Genotoxic stress (DNA damage)-inducing agents, by contrast, downregulate TRB3 expression and appear to do so through both p53-dependent and -independent mechanisms. To the best of our knowledge, TRB3 is the first gene that is upregulated by ER stress and downregulated following genotoxic stress. Collectively, these findings highlight the importance of stress-specific signaling cascades as well as point out the seemingly divergent roles that TRB3 may play in the cellular stress response.
Corcoran
Chad A
CA
Department of Pharmacology, State University of New York, Upstate Medical, Syracuse, New York 13210, USA.
Luo
Xiuquan
X
He
Qin
Q
Jiang
Changying
C
Huang
Ying
Y
Sheikh
M Saeed
MS
D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D004249:DNA Damage; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism / Q000502:physiology* / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D019284:Thapsigargin / Q000494:pharmacology
D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D012097:Repressor Proteins; C474831:TRIB3 protein, human; D019284:Thapsigargin; D017346:Protein Serine-Threonine Kinases