Ask about this productRelated genes to: GSK3B antibody
- Gene:
- GSK3B NIH gene
- Name:
- glycogen synthase kinase 3 beta
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 3q13.33
- Locus Type:
- gene with protein product
- Date approved:
- 1997-05-15
- Date modifiied:
- 2016-10-05
Related products to: GSK3B antibody
Related articles to: GSK3B antibody
- Macroautophagy/autophagy is a critical process for maintaining cellular homeostasis and has emerging implications in cancer biology. DRAM2 (DNA damage regulated autophagy modulator 2), a transmembrane protein enriched at lysosomal membranes, has been implicated in autophagy regulation; however, the upstream mechanisms governing its trafficking and function remain unclear. In this study, we identified RPS6KA3/RSK2, a stress-responsive kinase downstream of the MAPK pathway, as a novel upstream kinase of DRAM2. RPS6KA3/RSK2 interacted with and phosphorylated DRAM2 at Ser263 within its cytosolic tail. This phosphorylation was required for AP3D1/AP-3-dependent trafficking of DRAM2 to the late endosomal-lysosomal pathway, thereby facilitating autolysosome formation and sustaining autophagic flux. In contrast, the non-phosphorylatable DRAM2 mutant failed to bind AP3D1/AP-3, exhibited defective lysosomal trafficking, and was partially redistributed toward plasma membrane-proximal compartments, where it enhanced exosome secretion. Bioinformatic analyses revealed a strong positive correlation between RPS6KA3/RSK2 and DRAM2 expression in melanoma tissues, and elevated DRAM2 expression was associated with poor patient prognosis. Depletion of RPS6KA3/RSK2 or DRAM2 impaired autophagic flux and inhibited melanoma cell proliferation. Similarly, expression of the DRAM2 mutant suppressed melanoma progression in vitro and in vivo by disrupting autophagy. Moreover, DRAM2 protein levels were elevated in skin cancer tissues compared to normal tissues. Collectively, our findings uncover a phosphorylation-dependent trafficking switch that bifurcates DRAM2 function between autophagy and exosome secretion, and establish the RPS6KA3/RSK2-DRAM2 axis as a critical regulator of melanoma progression. This signaling pathway may represent a promising therapeutic target for autophagy-associated malignancies. AGC: protein kinase A, G, and C families; AP-3: adaptor protein 3; CD: cytosolic domain; CSNK2/CK2: casein kinase 2; co-IP: co-immunoprecipitation; CQ: chloroquine; CREB: cAMP responsive element binding protein; CTKD: C-terminal kinase domain; DRAM2: DNA damage regulated autophagy modulator 2; EBSS: Earle's balanced salt solution; ESCRT: endosomal sorting complexes required for transport; GEPIA: gene expression profiling interactive analysis; GPS: global positioning system; GRK7: G protein-coupled receptor kinase 7; GSK3B: glycogen synthase kinase 3 beta; IP-MS: immunoprecipitation-mass spectrometry; LAMP1: lysosome associated membrane protein 1; LAMP2: lysosome associated membrane protein 2; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MAPK: mitogen-activated protein kinase; MVB: multivesicular body; NTA: nanoparticle tracking analysis; NTKD: N-terminal kinase domain; PI4K2: phosphatidylinositol 4-kinase type 2 alpha; PRKAA2: protein kinase AMP-activated catalytic subunit alpha 2; RPS6KA3/RSK2: ribosomal protein S6 kinase A3; SKCM: skin cutaneous melanoma; SQSTM1: sequestosome 1. - Source: PubMed
Publication date: 2026/05/03
Lee Ga-EunNam Soo-BinMoon EunyoungHuh Yang HoonPark Hye SunNa SeungjinKim Jin YoungHan Eun HeeCho HanaChoi Jung HoonCho Yong-YeonBang GeulLee Cheol-Jung - Ferroptosis exerts a recognized role in the pathogenesis of acute kidney injury (AKI) and is considered a critical target for improving its prognosis. Emerging evidence indicates that ferroptosis serves a pivotal role in pathogenesis of AKI and targeting ferroptosis provides a promising therapeutic strategy in treatment of AKI. In the present study, ligustroflavone (LIG), which is a flavonoid with oral activity extracted from , was found to inhibit ferroptosis through activation of nuclear factor erythroid 2‑related factor 2 (NRF2) via inhibition of GSK3β and ., cisplatin (CDDP) and ischemia‑reperfusion injury (IRI)‑induced murine models of AKI were constructed to evaluate the possible effects of LIG. , the protective effects of LIG were assessed in cultured mouse renal proximal tubular epithelial cells (TKPTs). Immunostaining, reverse transcription‑quantitative PCR, western blot and lipid peroxidation assays were performed to detect renal tubular injury and ferroptosis. The results of the present study demonstrated that LIG administration significantly ameliorated CDDP or IRI induced renal damage in mice. Additionally, administration of LIG significantly ameliorated lipid peroxide accumulation and inhibited ferroptosis in the kidneys of AKI mice. , LIG treatment markedly ameliorated CDDP‑induced lipid peroxidation and ferroptosis in cultured TKPTs via GSK3β inhibition and NRF2 activation. Furthermore, knockout of GSK3β also protected against CDDP‑induced cell death and LIG exerted no additional protective effects in GSK3β‑knockout TKPTs. Together, the present findings offer a new potential strategy for AKI therapies by targeting ferroptosis. - Source: PubMed
Publication date: 2026/04/30
Song JiayuWang LongWang YaruMeng JieSheng JingyiZhao YongfengXu San YanLei JuanCai FangfangYang Yunwen - To investigate the effect and potential mechanism of blueberry anthocyanins(BA) in enhancing the chemosensitivity of colon cancer cells to oxaliplatin(OXA). - Source: PubMed
Yu XiaolanLiu JiarenGao HaiyanLiu Yan - Carnosine, an imidazole dipeptide, has potential for treating neurodegenerative diseases, including Parkinson's disease. However, carnosine-degrading enzymes limit its bioavailability. In this study, we established a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced Parkinson's disease and intranasally administered balenine, a carnosine analog featuring a methylated imidazole that is resistant to degradation enzymes, to target the brain via the olfactory epithelium. MPTP + balenine-treated mice demonstrated improved recognition scores in the object location test. They also exhibited a significantly increased tyrosine hydroxylase-positive cells and reduced expression of glial fibrillary acidic protein, an inflammatory marker, indicating that balenine mitigated neurodegenerative damage and inflammation in mice with MPTP-induced Parkinson's disease. Proteomic analysis revealed that activation of the KEAP1-NFE2L2 pathway, neddylation, and GSK3B and BTRC:CUL1-mediated degradation of NFE2L2. Collectively, these results highlight the efficacy of intranasal drops of balenine in Parkinson's disease and their potential to improve neurodegenerative disease prognosis. - Source: PubMed
Publication date: 2026/04/16
Chukai YusakuArisumi KonatsuYasunaga GentaSakai HirokiTatara YotaKasai ShuyaYamashita TetsuroIshiyama EriKiyokawa KokoroOzaki Taku - The dual-specificity, tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is intensively studied because of its implication in numerous human diseases (Down syndrome, Alzheimer's disease, type 2 diabetes, myocardial infarction, various cancers and leukaemia, etc.). Several GWAS studies have identified DYRK1A as a risk factor for Parkinson's disease (PD). DYRK1A indeed phosphorylates at least 20 proteins clearly involved in PD: AMPH, CASP9, DYN1, FOXO, GSK3B, MAP1B, MAPT, MEF2D, NFAT, TP53, PRKN, PLK2, RABs, RCAN1, SEPT4, SNCA, STAT3, SYNJ1, TOM70, WASL. Several other proteins involved in PD interact with DYRK1A: calpains, DSCAM, REST/NRSF, 14-3-3. DYRK1A is involved in axonal transport, neural stem cells proliferation and differentiation, and neuroinflammation. A few DYRK1A inhibitors have been tested on PD models, generally showing protective effects. The overall picture provided by this comprehensive review on the links between DYRK1A and PD advocates for more fundamental studies to understand how DYRK1A participates to the onset and development of PD and dementia with Lewy bodies (DLB), two closely related disorders. It also encourages the evaluation of well-characterized pharmacological modulators of DYRK1A as therapeutic approaches to various aspects of PD and DLB. - Source: PubMed
Publication date: 2026/04/14
Meijer LaurentLindberg Mattias FHogrel GaëlleKhor Bernard