Skin cancer is the most frequent form of malignancy in the world, and UV radiation is the primary environmental carcinogen responsible for its development. Herein we demonstrate that Gadd45a is a critical factor protecting the epidermis against UV radiation-induced tumorigenesis by promoting damaged keratinocytes to undergo apoptosis and/or cell cycle arrest, two crucial events that prevent the...

High-grade gliomas are severe tumors with poor prognosis. An R132H mutation in the isocitrate dehydrogenase (IDH1) gene prolongs the life of glioma patients. In this study, we investigated which genes are differentially regulated in IDH1 wild type (IDH1WT) or IDH1 R132H mutation (IDH1R132H) glioblastoma cells. Growth arrest and DNA-damage-inducible protein (GADD45A) was downregulated and microR...

Ionizing radiation (IR) therapy is one of the most commonly used treatments for cancer patients. The responses of tumor cells to IR are often tissue specific and depend on pathway aberrations present in the tumor. Identifying molecules and mechanisms that sensitize tumor cells to IR provides new potential therapeutic strategies for cancer treatment. In this study, we used two genetically engine...

OBJECTIVE Demethylation of CD11a and CD70 regulatory regions in CD4+ T cells contributes to the development of autoreactivity and overstimulation of autoantibodies. Because growth arrest and DNA damage-induced 45alpha (GADD45alpha) reduces epigenetic silencing of genes by removing methylation marks, this study examined whether the gadd45A gene could contribute to autoimmunity by promoting DNA d...

MicroRNAs (miRNAs) play crucial roles in the establishment of pluripotent state by controlling pluripotent network. However, the molecular mechanisms controlling miRNAs during somatic cell reprogramming remain obscure. In this study, we show Gadd45a (growth arrest and DNA-damage-inducible protein 45a) enhances reprogramming by activating miR-295. Furthermore, we show that Gadd45a binds the prom...

Diverse stresses including starvation and muscle disuse cause skeletal muscle atrophy. However, the molecular mechanisms of muscle atrophy are complex and not well understood. Here, we demonstrate that growth arrest and DNA damage-inducible 45a protein (Gadd45a) is a critical mediator of muscle atrophy. We identified Gadd45a through an unbiased search for potential downstream mediators of the s...

The Gadd45a stress sensor gene is a member in the Gadd45 family of genes that includes Gadd45b & Gadd45g. To investigate the effect of GADD45A in the development of CML, syngeneic wild type lethally irradiated mice were reconstituted with either wild type or Gadd45a null myeloid progenitors transduced with a retroviral vector expressing the 210-kD BCR-ABL fusion oncoprotein. Loss of Gadd45a was...

Gadd45a plays a pivotal role as a stress sensor that modulates cellular responses to various stress stimuli including oncogenic stress. We reported that the stress sensor Gadd45a gene functions as a tumor suppressor in Ras-driven breast tumorigenesis via increasing JNK-mediated apoptosis and p38-mediated senescence. In contrast, here, we show that Gadd45a promotes Myc-driven breast cancer by ne...

Growth arrest and DNA-damage-inducible protein 45 (Gadd45) family members have been implicated in DNA demethylation in vertebrates. However, it remained unclear how they contribute to the demethylation process. Here, we demonstrate that Gadd45a promotes active DNA demethylation through thymine DNA glycosylase (TDG) which has recently been shown to excise 5-formylcytosine (5fC) and 5-carboxylcyt...

The growth arrest and DNA damage-inducible protein 45alpha (GADD45a) gene is responsive to a variety of DNA-damaging agents. It is known that induction of the GADD45a gene is regulated in a p53-dependent manner after ionizing irradiation. Our previous study showed that X-ray irradiation increased the transcription rate of the GADD45a gene much earlier than the maximum accumulation of stabilized...