| 2015 |
HMBOX1 physically interacts with MT2A (identified by yeast two-hybrid and confirmed by co-immunoprecipitation), and this interaction elevates intracellular free zinc levels; knockdown of MT2A abolishes HMBOX1-mediated zinc elevation, anti-apoptotic, and pro-autophagic effects in vascular endothelial cells. |
Yeast two-hybrid, co-immunoprecipitation, MT2A knockdown with phenotypic readout, zinc chelation rescue experiment |
Scientific reports |
Medium |
26456220
|
| 2017 |
XAF1 directly interacts with MT2A and facilitates its lysosomal degradation, leading to elevation of free intracellular zinc, subsequent p53 activation, and XIAP inactivation, thereby switching stress response toward apoptosis. A MT2A-binding-deficient XAF1 mutant fails to elevate free zinc, confirming the interaction is required for this mechanism. Conversely, MT2A destabilizes XAF1 via the lysosomal pathway under cytostatic stress, establishing mutual antagonism. |
Co-immunoprecipitation, domain-mutant XAF1 (binding-deficient), lysosomal degradation assays, intracellular zinc measurement, xenograft models, loss-of-function experiments |
Proceedings of the National Academy of Sciences of the United States of America |
High |
28507149
|
| 2006 |
Recombinant human MT2A expressed in E. coli retains intact metal-binding ability, hydroxyl radical scavenging ability, and protective activity against DNA damage caused by UVC radiation, establishing these as intrinsic biochemical activities of the protein. |
In vitro biochemical assays: metal-binding, hydroxyl radical scavenging, DNA damage protection assay with UVC-irradiated purified recombinant protein |
Protein expression and purification |
Medium |
17224279
|
| 2014 |
EOLA1 interacts with MT2A (identified by yeast two-hybrid screening), and MT2A plays a key role in LPS-induced IL-6 expression in HUVECs; EOLA1 acts as a negative regulator of LPS response by regulating MT2A activity. |
Yeast two-hybrid, knockdown of EOLA1 and MT2A with IL-6 and apoptosis readouts in HUVECs |
Molecular and cellular biochemistry |
Medium |
24916366
|
| 2015 |
EOLA1 association with MT2A negatively regulates LPS-induced VCAM-1 expression in ECV304 endothelial cells; MT2A knockdown reduces LPS-induced VCAM-1 production, placing MT2A as a positive regulator of VCAM-1 in this inflammatory pathway. |
Knockdown of EOLA1 and MT2A, overexpression of EOLA1, VCAM-1 measurement in LPS-stimulated ECV304 cells |
International journal of inflammation |
Low |
26881174
|
| 2020 |
MT2A interacts with BARD1 and BRCA1 (confirmed by co-immunoprecipitation and co-localization by immunofluorescence) and positively regulates BARD1/BRCA1 levels; BARD1 overexpression partially restores Oxaliplatin resistance lost upon MT2A knockdown in colorectal cancer cells, placing MT2A upstream of BARD1/BRCA1 in chemoresistance. |
Co-immunoprecipitation, immunofluorescence co-localization, MT2A knockdown and overexpression with viability/resistance readouts, BARD1 rescue experiment |
Cell biochemistry and biophysics |
Medium |
32638210
|
| 2022 |
MT2A overexpression promotes phosphorylation of MST1, LATS2, and YAP1, thereby activating the Hippo signaling pathway and inhibiting colorectal cancer cell proliferation and liver metastasis; specific MST1/2 inhibitors abolish this phosphorylation and rescue proliferation, placing MT2A upstream of the MST1/LATS2/YAP1 axis. |
Western blotting for Hippo pathway phosphorylation, MT2A overexpression and knockdown in cells, xenograft and liver metastasis animal models, MST1/2 inhibitor rescue experiment, immunohistochemistry |
Cancer cell international |
Medium |
35642057
|
| 2021 |
MT2A overexpression in HL60 AML cells induces apoptosis and G2/M cell cycle arrest associated with downregulation of p-IκB-α and cyclin D1 and upregulation of IκB-α, placing MT2A as a negative regulator of the NF-κB pathway; MT2A knockdown conversely increases proliferation. |
Lentiviral MT2A overexpression, shRNA knockdown, flow cytometry, Western blotting for NF-κB pathway components, cell viability assays in HL60 cells |
International journal of medical sciences |
Medium |
34220318
|
| 2022 |
CD69 inhibits activin A-induced erythroid differentiation via MT2A; activin A reduces MT2A expression through p38MAPK, and MT2A knockdown reduces CD69's ability to suppress erythroid marker expression and sensitization to imatinib in K562 CML cells, placing MT2A downstream of CD69 in this differentiation pathway. |
MT2A knockdown, CD69 overexpression, p38MAPK inhibition (SB203580), erythroid marker expression, growth inhibition and apoptosis assays in K562 and BCR-ABL+ CD34+ cells |
Experimental cell research |
Medium |
35643179
|
| 2023 |
HSF1 binds the MT2A promoter to transcriptionally activate MT2A; RING1 (an E3 ubiquitin ligase) binds HSF1 and induces its proteasome-dependent degradation, thereby suppressing MT2A transcription and causing cell cycle arrest and apoptosis in breast cancer cells. Ectopic MT2A expression rescues the anti-proliferative effects of RING1, placing MT2A downstream of the RING1-HSF1 axis. |
Co-immunoprecipitation (RING1-HSF1), ChIP (HSF1 on MT2A promoter), proteasome inhibitor experiments, MT2A ectopic overexpression rescue, xenograft models, Western blotting |
Experimental cell research |
Medium |
37797799
|
| 2025 |
Artesunate (AS) directly binds MT2A (validated by HuProt 20K human proteome microarray and surface plasmon resonance), upregulates MT2A in astrocytes, reduces intracellular Cu2+ levels, and inhibits cuproptosis (FDX1, CTR1, lip-DLAT regulation); MT2A-Lys-31 is identified as a key functional site. MT2A knockdown abolishes AS-mediated neuroprotection and copper reduction. |
Human proteome microarray (HuProt 20K), surface plasmon resonance (SPR), MT2A knockdown, site-directed mutagenesis (Lys-31), copper ion measurements, cuproptosis marker assessment, in vivo 6-OHDA Parkinson's disease model |
Pharmacological research |
High |
40754045
|
| 2025 |
Under hypoxia, MT2A translocates to mitochondria in a copper-ion-dependent manner and interacts with the tetrameric form of PKM2 to maintain PKM2 enzymatic activity, thereby promoting glycolysis and oxidative phosphorylation in breast cancer cells. |
Mitochondrial proteomics, co-immunoprecipitation (MT2A-PKM2 tetrameric form), subcellular fractionation, copper ion manipulation, glycolysis and OXPHOS functional assays, MT2A knockdown with tumor growth readout |
Cell insight |
Medium |
41211480
|
| 2025 |
MT2A overexpression in HUVECs alleviates copper overload (CPO)-induced mitochondrial dysfunction and cytotoxicity; in a rat chronic ischemia model, MT2A overexpression reduces DLAT accumulation and mitochondrial abnormalities and promotes angiogenesis, establishing a copper-mitochondria regulatory mechanism for MT2A in ischemic angiogenesis. |
MT2A overexpression in HUVECs (in vitro copper overload model), rat 2VO+EMS in vivo model, mitochondrial morphology and activity assays, CD31 immunostaining, cuproptosis marker analysis (DLAT, FDX1, SDHB), cerebral blood perfusion measurement |
Journal of translational medicine |
Medium |
39915841
|
| 2024 |
MT2A overexpression in hypoxia-exposed dorsal root ganglion neurons inhibits apoptosis by inactivating p38 MAPK, and MT2A co-localizes with neurons (but not microglia or astrocytes) in rat DRG tissues, establishing MT2A as a neuronal anti-apoptotic regulator acting through the p38 MAPK pathway in neurogenic intermittent claudication. |
Lentivirus-mediated MT2A overexpression in primary neurons, hypoxia-induced cell damage model, co-localization immunostaining, apoptosis assays, p38 MAPK activation measurements, rat cauda equina compression model |
Human cell |
Medium |
38546949
|
| 2019 |
TUG1 lncRNA recruits EZH2 to the MT2A promoter to epigenetically suppress MT2A transcription; ChIP experiments confirmed EZH2 binding to the MT2A promoter, and TUG1 knockdown reduced this binding, de-repressing MT2A expression. [NOTE: This paper was subsequently retracted (PMID:34992381), so this finding should be treated with caution.] |
RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), TUG1 knockdown, MT2A expression analysis |
OncoTargets and therapy |
Low |
30787623
|
| 2023 |
GHET1 lncRNA recruits EZH2 and LSD1 to the MT2A promoter, reducing H3K27me3 and H3K4me2 occupancy to epigenetically suppress MT2A transcription; MT2A knockdown reverses GHET1 inhibition of trophoblast phenotypes, establishing MT2A as a downstream effector of GHET1 in extravillous trophoblast biology. |
RNA immunoprecipitation (RIP), RNA pull-down, chromatin immunoprecipitation (ChIP) for histone marks, MT2A knockdown rescue experiments, proliferation and migration assays |
Molecular reproduction and development |
Medium |
37548351
|