CHOP is induced by a number of stress stimuli.  All of these stimuli lead to the activation of one of the 4 kinases that phosphorylate eIF2a, i.e., GCN2, PERK, PKR and HRI. Each kinase is activated in response to specific set of stress stimuli.  Activation of these kinases leads to phosphorylation of eIF2a, the induction of ATF4 transcription factor and ultimately the induction of CHOP. This pathway is called the integrated stress response (ISR). 

There are a number of reports suggesting that CHOP induction is essential for stress-induced apoptosis.  Furthermore, it is suggested that CHOP is responsible for the regulation of Bcl-2 family of proteins and that is the mechanism by which it induces cell death.  However, accumulating data  from the CHOP deficient cells has shown that the rate of stress-induced (ER stress in particular) cell death is not affected in these cells. This suggest that CHOP is not required nor is essential for stress-induced apoptosis.  However, overexpression of CHOP is toxic in several cell lines. Some of the recent papers suggest that CHOP indirectly induces cell death through regulation of ER redox status and also through the reversal of the translational block.  

So, although CHOP is induced by the ISR, it is by no means a marker of apoptosis. You should still stick with the classical markers of apoptosis and use 2-3 of these in your studies, e.g., caspase enzymatic activity (DEVDase activity), or caspase-3/PARP cleavage, annexin V staining, morphological assessment (microscopy) etc.

Please be aware that CHOP can be induced by oxidative stress and ROS.  Oxidants / ROS can cause rapid inactivation of the cysteine residue in the active site of caspases leading to their inactivation and targeting them for degradation.  So if your compound is inducing ROS, it may induce CHOP, inactivate caspases and induce necrosis/necroptosis. 

CHOP is induced by a number of stress stimuli.  All of these stimuli lead to the activation of one of the 4 kinases that phosphorylate eIF2a, i.e., GCN2, PERK, PKR and HRI. Each kinase is activated in response to specific set of stress stimuli.  Activation of these kinases leads to phosphorylation of eIF2a, the induction of ATF4 transcription factor and ultimately the induction of CHOP. This pathway is called the integrated stress response (ISR). 

There are a number of reports suggesting that CHOP induction is essential for stress-induced apoptosis.  Furthermore, it is suggested that CHOP is responsible for the regulation of Bcl-2 family of proteins and that is the mechanism by which it induces cell death.  However, accumulating data  from the CHOP deficient cells has shown that the rate of stress-induced (ER stress in particular) cell death is not affected in these cells. This suggest that CHOP is not required nor is essential for stress-induced apoptosis.  However, overexpression of CHOP is toxic in several cell lines. Some of the recent papers suggest that CHOP indirectly induces cell death through regulation of ER redox status and also through the reversal of the translational block.  

So, although CHOP is induced by the ISR, it is by no means a marker of apoptosis. You should still stick with the classical markers of apoptosis and use 2-3 of these in your studies, e.g., caspase enzymatic activity (DEVDase activity), or caspase-3/PARP cleavage, annexin V staining, morphological assessment (microscopy) etc.

Please be aware that CHOP can be induced by oxidative stress and ROS.  Oxidants / ROS can cause rapid inactivation of the cysteine residue in the active site of caspases leading to their inactivation and targeting them for degradation.  So if your compound is inducing ROS, it may induce CHOP, inactivate caspases and induce necrosis/necroptosis. 

CHOP is mostly known as a pro-apoptotic factor mainly induced by ER stress. However, this transcription factor is also involved in many physiological adaptive processes, and different  studies support an anti-apoptotic role of CHOP in

 B-cells and other cell lineages. In any case, as indicated by Dr. Salami, CHOP should not be considered as a marker of apoptosis.

See this interesting paper related to your question: http://ac.els-cdn.com/S0161589009008591/1-s2.0-S0161589009008591-main.pdf?_tid=1a4d3104-d3a4-11e4-ac4d-00000aab0f6b&acdnat=1427366429_18fc2c40b8d2bbd176fb61b1ddcbd728

Dr. Samali thanks  for explanation in detail. I think CHOP expression is bit difficult to understand as in my case I saw decrease in p-EIF2 alpha, Increase in viability but also increase in CHOP so could be possible CHOP activation downstream of p-EIF2 alpha is not definitive phenomenon in my case at-least. But looking at ROS generation will definitely as interesting study to do so it is on the list.

 Dr. Gallego thanks for the publication it seems like CHOP role vary from one cell lineage to other. 

CHOP is NOT a marker of apoptosis

it suggests a potential pathway for cell death that is dependent on CHOP expression. If you see cell death and CHOP expression you can only assess its role by using CHOP KO cells and assessing effects on death.