GADD45A

Last update 08 May 2025

Basic Info

Synonyms

DDIT-1, DDIT1, DNA damage-inducible transcript 1 protein

+ [4]

Introduction

In T-cells, functions as a regulator of p38 MAPKs by inhibiting p88 phosphorylation and activity (By similarity). Might affect PCNA interaction with some CDK (cell division protein kinase) complexes; stimulates DNA excision repair in vitro and inhibits entry of cells into S phase.

100 Clinical Results associated with GADD45A

100 Translational Medicine associated with GADD45A

0 Patents (Medical) associated with GADD45A

1,718

Literatures (Medical) associated with GADD45A

01 Jul 2025·Anti-Cancer Agents in Medicinal Chemistry

Unveiling the Potential of S4 on Non-small Cell Lung Cancer Cells: Impact on Proliferation, Apoptosis, Senescence, and Metabolome Profile

Article

Author: Yavuz, Mervenur ; Demircan, Turan ; Bölük, Aydın

Background:Lung cancer is a highly aggressive tumor with limited therapeutic options. The misregulation of Androgen Receptor (AR) signaling has been observed in lung cancer. Therefore, inhibiting AR signaling is a promising strategy for treating lung cancer.Objective:Selective Androgen Receptor Modulators (SARMs) are small molecule drugs with a high affinity for the AR. S4, a member of SARMs was potentially positioned as a promising therapeutic agent in A549 lung cancer cells owing to its high bioavailability, lesser side effects, and novelty in cancer.Methods:We employed several techniques to investigate the potential anti-carcinogenic effect of S4 on A549 cells at cellular level. The cytotoxicity of S4 was investigated thorough MTT, and the IC50 value was identified as 0.22 mM. Then, the anchorage-dependent and -independent colonization of cells were assessed by colony formation and soft agar assays, respectively. Additionally, migration capacity, apoptosis, proliferation, senescene, cell-cycle progression of cells was examined thoroughly. In addition, gene expression profile and metabolome signature were explored via qRT-PCR and metabolomics, respectively to provide molecular links for S4 mode of action.Results:Our findings demonstrate that S4 inhibited growth, migration, and proliferation while inducing apoptosis. S4 significantly upregulated the BAX, CDKN1A, PUMA, and GADD45A genes while downregulating MKI67, BIRC5, and PCNA expression. S4 treatment drastically altered the metabolome signature, and enrichment of cancer related pathways by altered metabolites was noteworthy.Conclusion:We report the first study evaluating the potential anti-carcinogenic effects of S4 on lung cancer invitro which would bridge the gap on the utility of SARMs as inhibitors of lung cancer. Our results suggest that S4 could be considered as a promising drug candidate to test further for lung cancer treatment.

01 Apr 2025·Advanced Science

CircDNA2‐Educated YTHDF2 Phase Separation Promotes PM_2.5‐Induced Malignant Transformation Through the Blunting of GADD45A Expression

Article

Author: Xu, Jie ; Xu, Duo ; Yin, Lijia ; Chen, Rui ; Ling, Zhi ; Wu, Shenshen

AbstractSubstantial epidemiological evidence suggests a significant correlation between particulate matter 2.5 (PM2.5) and lung cancer. However, the mechanism underlying this association needs to be further elucidated. Circular RNAs (circRNAs) have emerged as an important topic in the field of epigenetics and are involved in various cancers. This study aimed to explore the molecular basis of PM2.5‐induced lung cancer from an epigenetic perspective and identify potential biomarkers. Initially, the construction of a chronic PM2.5 exposure model confirmed that PM2.5 exposure promoted the malignant transformation of human bronchial epithelial (HBE) cells. Mechanistically, abnormally upregulated circDNA2 inhibited the tumor suppressor gene growth arrest and DNA damage 45 alpha (GADD45A) mRNA in an N6‐methyladenosine (m6A)‐dependent manner, mediated by YTH N6‐Methyladenosine RNA Binding Protein F2 (YTHDF2) after PM2.5 exposure. Further analyses revealed that circDNA2 can specifically bind to the YTHDF2 LC domain to promote YTHDF2 protein liquid–liquid phase separation (LLPS), providing sufficient evidence linking LLPS and particulate pollutant‐induced tumorigenesis. In conclusion, this study provides new insights into the role of circDNA2 in PM2.5‐induced lung cancer and confirms its clinical value as a potential prognostic biomarker for lung cancer.

01 Apr 2025·Circulation: Genomic and Precision Medicine

DNA Damage Response and Repair Genes and Anthracycline-Induced Cardiomyopathy in Childhood Cancer Survivors: A Report From the Children’s Oncology Group and the Childhood Cancer Survivor Study

Article

Author: Cheng, Changde ; Landier, Wendy ; Hudson, Melissa M. ; Armstrong, Gregory T. ; Burridge, Paul W. ; Hawkins, Douglas S. ; Armenian, Saro H. ; Chow, Eric J. ; Trainor, Patrick J. ; Sharafeldin, Noha ; Neglia, Joseph P. ; Hageman, Lindsey ; Sapkota, Yadav ; Ginsberg, Jill P. ; Wang, Fan ; Zhou, Liting ; Wang, Xuexia ; Singh, Purnima ; Bhatia, Smita ; Yasui, Yutaka ; Cejas, Romina B.

BACKGROUND:Anthracyclines induce cardiotoxicity via DNA double-strand breaks and reactive oxygen species formation, resulting in cardiomyocyte dysfunction. The role of DNA damage response/repair (DDR) genes in anthracycline-induced cardiomyopathy remains unstudied.METHODS:We conducted a gene-based and pathway-based analysis to examine the main effect and gene-anthracycline interaction effect between DDR genes and anthracycline-induced cardiomyopathy. A discovery analysis performed with a matched case-control set of anthracycline-exposed non-Hispanic White childhood cancer survivors from Children's Oncology Group-ALTE03N1 (113 cases; 226 controls) was replicated using a cohort of anthracycline-exposed non-Hispanic White childhood cancer survivors from the Childhood Cancer Survivor Study cohort (n=1658; 97 cases). Functional analyses were performed by examining the response to doxorubicin of human-induced pluripotent stem cell-derived cardiomyocytes with CRISPR/Cas9-mediated knockout of prioritized genes.RESULTS: Successfully replicated DDR genes demonstrating main-effect association included FANCC ( P =0.037) and XRCC5 ( P =0.001) and demonstrated gene-anthracycline interaction included MGMT ( P =0.041). Knockouts of FANCC and MGMT in human-induced pluripotent stem cell-derived cardiomyocytes demonstrated significant resistance to doxorubicin, suggesting that these genes play a role in anthracycline-induced cardiotoxicity. Successfully replicated DDR pathways demonstrating main-effect association included base excision repair ( P =2.7×10 −4 ); role of BRCA1 in DDR ( P =9.2×10 −5 ); p53 signaling ( P <1×10 −16 ); role of checkpoint kinases proteins in cell cycle checkpoint control ( P <1×10 −16 ); mismatch repair ( P <10 −16 ); and double-strand break repair by homologous recombination ( P <1×10 −16 ). Successfully replicated DDR pathways demonstrating significant interaction effects included role of BRCA1 in DDR ( P =1.4×10 −4 ); p53 signaling ( P< 1×10 −16 ); the role of checkpoint kinases proteins in cell cycle checkpoint control ( P <1×10 −16 ); mismatch repair ( P <1×10 −16 ); cell cycle: G2/M DNA damage checkpoint regulation ( P =0.002); double-strand break repair by homologous recombination ( P =0.009); GADD45 signaling ( P =4.8×10 −4 ); and cell cycle control of chromosomal replication ( P =4.5×10 -4 ). CONCLUSIONS:These findings provide evidence for the role of DDR genes and pathways in anthracycline-induced cardiomyopathy and provide a framework for targeted therapeutic interventions.

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GADD45A

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