When the researchers knocked out
ATF4 in cells or mice they found tumours continued to increase the amount of 4E-BP - and eventually died from stress.
ATF4 Was Increased in Mouse Corneas Infected by Intrastromal Injection.
[70] Similarly,
ATF4 being transcriptional regulator of the cellular hypoxic response to the UPR also showed resistance to bortezomib which actually a UPR-apoptosis mediator through autophagy induction as a survival key in HCC.
Alteration of PERK and
ATF4 signaling is responsible for ER stress-associated redox imbalance and affects the disulfide bond formation (ERO1, endoplasmic reticulum oxidoreductin; PDI, protein disulfide isomerase) that influences antioxidant activation in ER [2].
ER stress caused by the accumulation of unfolded proteins triggers the unfolded protein response (UPR) which in turn modulates both transcription and translation of key regulators (e.g.,
ATF4) of the cellular stress response [37].
33'-diindolylmethane induces activating transcription factor 3 (ATF3) via
ATF4 in human colorectal cancer cells.
Redfern, "Regulation of endoplasmic reticulum stress-induced cell death by
ATF4 in neuroectodermal tumor cells," Journal of Biological Chemistry, vol.
Meanwhile, upregulation of
ATF4 and CHOP, known as a hallmark of one of the three pathways of endoplasmic reticulum stress (ER stress) response, was also observed.
To investigate whether UPR, especially CHOP10 induction, is involved in the suppression of terminal adipogenesis by [iAs.sup.3+], the expression of
ATF4 and CHOP10 were measured in 3T3-L1 cells.