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Spotlight on Molecular Targeted Therapy

Myeloid Differentiation (MyD)/Growth Arrest DNA Damage (GADD) genes in tumor suppression, immunity and inflammation

Abstract

Myeloid differentiation (MyD) primary response and growth arrest DNA damage (Gadd) genes comprise a set of overlapping genes, including known (IRF-1, EGR-1, Jun) and novel (MyD88, Gadd45α, MyD118/Gadd45β, GADD45γ, MyD116/ Gadd34) genes, that have been cloned by virtue of being co-ordinately induced upon the onset of terminal myeloid differentiation and following exposure of cells to stress stimuli. In recent years it has become evident that MyD/Gadd play a role in blood cell development, where they function as positive regulators of terminal differentiation, lineage-specific blood cell development and control of blood cell homeostasis, including growth inhibition and apoptosis. MyD/Gadd are also involved in inflammatory responses to invading micro-organisms, and response to environmental stress and physiological stress, such as hypoxia, which results in ischemic tissue damage. An intricate network of interactions among MyD/GADD genes and gene products appears to control their diverse functions. Deregulated growth, increased cell survival, compromised differentiation and deficiencies in DNA repair are hallmarks of malignancy and its progression. Thus, the role MyD/Gadd play in negative growth control, including cell cycle arrest and apoptosis, and in DNA repair, make them attractive molecular targets for tumor suppression. The role MyD/Gadd play in innate immunity and host response to hypoxia also make these genes and gene products attractive molecular targets to treat immunity and inflammation disorders, such as septic shock and ischemic tissue damage.

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Acknowledgements

I would like to thank Dr Arthur Balliet and Dr Arshad Amanullah for critical reading of the review.

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Liebermann, D., Hoffman, B. Myeloid Differentiation (MyD)/Growth Arrest DNA Damage (GADD) genes in tumor suppression, immunity and inflammation. Leukemia 16, 527–541 (2002). https://doi.org/10.1038/sj.leu.2402477

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