CHOP/GADD153 - A regulator and marker for ER-stress induced apoptosis

Mon, 08/17/2015 - 14:45

C/EBP homologous protein (CHOP) is a transcription factor that regulates apoptosis in response to cellular stress. CHOP also known as growth arrest and DNA damage 153 (GADD153) was first cloned because of its induction in response to genotoxic stress such as UV irradiation. CHOP has now been shown to be induced mainly by ER-stress (1). CHOP is normally expressed at low levels and localizes to the cytoplasm. Cellular stress triggers an upregulation of CHOP levels and accumulation in the nucleus where it can act as either a transcriptional repressor or activator (1). CHOP contains an N-terminal transcriptional activation domain and a C-terminal basic leucine zipper domain responsible for DNA binding (1). In the nucleus CHOP forms heterodimers with C/EBP family transcription factors to either enhance promoter binding or to inhibit their activity. In this manner CHOP regulates genes involved in cell survival and death (1). ER-stress induced apoptosis mediated through CHOP is implicated in various diseases including diabetes and neurodegeneration. In these cases inactivation of CHOP may provide a useful tool for blocking the enhanced apoptosis observed in these diseases (1).

CHOP/GADD153 antibodies have provided excellent tools to study ER-stress induced apoptosis. Lee et al. explored the use of autophagy and ER-stress related markers as prognostic indicators in hepatocellular carcinoma (2). In their study they performed immunohistochemisty using the CHOP/GADD153 antibody along with antibodies for LC3, Beclin 1, and GRP78 (2). While strong positive correlations with these markers were not observed, LC3 expression did correlate with good prognosis (2). Lin et al. used the CHOP/GADD153 antibody in their characterization of temozolomide, a chemotherapeutic drug used in the treatment of brain tumors (3). They monitored CHOP/GADD153 levels through western blotting to examine ER-stress induction in response to temozolomide (3). A group from the University of Washington sought to examine the role of hIAPP in the development of type II diabetes (4). Previous studies had shown induction of ER-stress by hIAPP expression. However, the authors of this study immunostained pancreatic islet cells with the CHOP/GADD153 antibody to show ER-stress is not induced at physiological levels of hIAPP (4). The Ron group at New York University identified carbonic anhydrase VI (CA-VI) as the first positively upregulated CHOP target gene (5). Using the CHOP/GADD153 antibody for western blotting the authors were able to show CHOP dependent induction of CA-VI (5). They then went on to show CHOP is present at the CA-VI promoter using in vitro footprinting assays.

Novus Biologicals offers CHOP/GADD153 reagents for your research needs including:


  1. 14685163
  2. 24282606
  3. 22745676
  4. 19352619
  5. 9858573

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