Molecular signaling network motifs provide a mechanistic basis for cellular threshold responses.
The upregulation of PARP by the combination of TNF-α and EGF suggests a protective response by chondrocytes as a certain cellular threshold for tolerance is exceeded.
We demonstrate that diminishing urokinase plasminogen activator (uPA) levels leads to decreased ERK1/2 survival signaling, thus lowering the cellular threshold to trigger TRAIL-induced apoptosis.
uPA depletion resulted in a ∼4-fold increase of sensitivity for triggering cell death upon TRAIL challenge, supporting the notion that diminishing uPA levels reduces the cellular threshold for triggering TRAIL-induced cell death.
Although mutations in DYT1 are associated with a rare form of heritable generalized dystonia, the native function of torsinA seems to be cytoprotective in maintaining the cellular threshold to endoplasmic reticulum (ER) stress.
Pre-clinical data on apoptosis-targeted agents suggest that their ultimate clinical use will be in combination with cytotoxics, in which an enforced reduction in the cellular threshold for apoptosis by the former should sensitise to the latter.
Because CRL4A regulates the cellular threshold of DNA repair and cell cycle checkpoint proteins, we investigated whether CUL4A affects DNA repair capacity and/or the onset of tumorigenesis induced by genotoxic insults [12].
However, an increase in ROS beyond a certain cellular threshold may lead to cell death through various mechanisms, such as activation of the JNK/p38-mediated signaling pathway, direct damage to the mitochondrial membrane, and release of cytochrome c [81]– [81].
The increasing interest in plant bioresources that can potentiate antioxidant systems is based on the notion that beyond the normal cellular threshold for apoptosis and cell death, such exogenous antioxidants could complement the cellular defence systems in countering H2O2-induced damage [ 1, 26, 27].
It is generally believed that low doses of TRAIL induce a poor apoptotic response and may generate resistance, whereas exposure to high levels of this cytokine results in extensive cell death, indicating the existence of a cellular threshold for triggering apoptosis (referred hereafter as 'sensitivity'sensitivity
