Negative growth regulatory protein
Growth-Arrest and DNA-damage inducible 45 genes have been implicated in stress signaling in response to physiological or environmental stressors, which results in either cell cycle arrest, DNA repair, cell survival and senescence, or apoptosis. GADD proteins acts as stress sensors and are mediated by physical interaction with cellular proteins such as PCNA, p21, cdc2/cyclinB1, p38 and JNK stress response kinase, that are implicated in cell cycle regulation and stress related responses. There are two isoforms of GADD45 known (GADD45a and GADD45b), myeloid enriched bone marrow cells from mouse deficient in GADD45a and GADD45b are more susceptible to apoptosis induced chemically or by UV radiation than wild type cells (1). These data suggest that GADD45 proteins are anti-apoptotic and increase the survival of hematopoietic cells following UV irradiation. The GADD45b deficient mouse also exhibit deficiencies in neuronal activity induced proliferation of neuronal progenitors and dendritic growth of new born neurons in adult hippocampus. GADD45b is required for activity-induced DNA demethylation of specific promotors and expression of corresponding genes critical for adult neurogenesis brain derived neurotrophic factors and fibroblast growth factor (2).
Electro-convulsive treatment ECT) of adult mice cuases a sustained up-regulation of hippocampal neurogenesis without any significant cell damage. ECT also up-regulated GADD45b, a known epigenetic regulator (2). The neuroprotective effect of GADD45b has been shown in retinal ganglion cells (RGC), GADD45b is up-regulated in RGCs in response to oxidative stress, aging and increasing ocular pressure. Using GADD45b SiRNA, the RGCs are protected from dying against different neuronal injury including oxidative stress, TNF alfa cytotoxicity and glutamate excitotoxicity in vitro, suggesting GADD45b is a component of an intrinsic neuroprotective mechanism in RGC in retina and perhaps in CNS (3). GADD45b is a neuronal activity-induced immediate early gene in mature hippocampal neurons (2). GADD45b also promotes hepatocyte survival during liver regeneration in mice by modulating the activity of JNK signaling, suggestingthat GADD45b may be a potential therapeutic target in liver disease (4). GADD45b is a 160 amino acid (20kDa) protein
The GADD45b-selective rabbit antibodies were generated against a C-terminal peptide epitope conserved in mouse, rat, human, chimp, and other species but not present in GADD45a subunit. GADD45b synthetic peptide was covalently modified to achieve desired antigenic properties and was conjugated to a carrier protein before used as immunogen to raise antibodies in rabbits. The GADD45b antibodies are affinity purified over immobilized immunogenic peptide affinity matrix and stabilized with preservatives for long-term storage. FabGennix will conjugate this antibody to secondary enzymes (alkaline phosphatase or horseradish peroxidase) and fluorophores at a nominal charge. FabGennix Int. Inc. stocks limited quantities of western blot positive controls for GADD45b in ready-to-use buffers and antigenic blocking peptide for immune-depletion assays for GADD-201AP antibody. FabGennix Int. Inc., has a wide range of antibodies and reagents for biomedical research community. For a complete listing please visit www. FabGenix.Com.
For research use only, not for diagnostic or therapeutic use.
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