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Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B)
- Target
- GADD45B
- Molecular classification
- Stress response protein, DNA damage response protein, Cell cycle regulator, Apoptosis regulator, Other (sometimes considered under transcriptional regulation)
01
Overview
GADD45B is a highly conserved, small (18 kDa) stress response protein rapidly induced following environmental or physiological stress—including DNA damage, oxidative stress, or cytokine stimulation. It mediates cell cycle arrest, apoptosis, and DNA repair chiefly via protein-protein interactions rather than enzymatic activity. GADD45B regulates the p38/JNK MAPK pathway, affecting both innate and adaptive immune responses, including myeloid cell recruitment, T and B cell differentiation, and cytokine production. It has been implicated as a therapeutic target and disease biomarker in a range of cancers, inflammatory, autoimmune, and neuropsychiatric conditions.
- Other names
- MyD118Growth arrest and DNA-damage-inducible betaNegative growth regulatory protein MyD118myeloid differentiation primary response protein MyD118GADD45BETADKFZP566B133GADD45Bgrowth arrest and DNA damage-inducible protein GADD45 beta
02
Mechanism of action
Indirect: activation or inhibition of the p38/JNK MAPK pathways via protein-protein interactions (e.g., with MTK1/MEKK4 kinase), cell cycle arrest, modulation of apoptosis and immune cell function
03
Biological functions
Stress sensingCell cycle arrestApoptosisDNA repairInnate and adaptive immune response regulation (immune cell recruitment, differentiation, cytokine modulation)Cell proliferationGenomic stability maintenance
04
Disease associations
Cancer (hematologic, lung, colorectal)InflammationAutoimmune disease (systemic lupus erythematosus, autoimmune lymphoproliferative syndrome, Graves’ disease, multiple sclerosis)Neuropsychiatric disorders (psychosis)Pulmonary fibrosis/inflammatory lung injury
05
Safety considerations
Targeting GADD45B may affect fundamental cell stress responses; risks include unwanted apoptosis, impaired cell cycle or immune function, and potentially exacerbating certain inflammatory or autoimmune conditions
06
Interacting drugs
No approved drugs specifically targeting GADD45B are reported; however, drugs that induce DNA damage (e.g., cytostatic agents, radiation, cadmium chloride) increase GADD45B expression
07
Biomarkers
Elevated GADD45B mRNA/protein levels may serve as biomarkers for cellular stress states, psychosis, autoimmune disease activity, and inflammatory disorders
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