Ask about this productRelated genes to: ATP2A2 Blocking Peptide
- Gene:
- ATP2A2 NIH gene
- Name:
- ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2
- Previous symbol:
- ATP2B, DAR
- Synonyms:
- SERCA2
- Chromosome:
- 12q24.11
- Locus Type:
- gene with protein product
- Date approved:
- 1990-09-10
- Date modifiied:
- 2016-02-10
Related products to: ATP2A2 Blocking Peptide
Related articles to: ATP2A2 Blocking Peptide
- Anthracycline-induced cardiotoxicity remains a major limitation in cancer therapy, with substantial inter-individual variability in susceptibility, including documented sex differences. However, the molecular basis underlying these disparities remains incompletely understood. In this study, we employed large-scale data-independent acquisition proteomics in a long-latency rat model of doxorubicin-induced cardiomyopathy to characterize early cardiac proteomic remodeling. Longitudinal echocardiography demonstrated a significantly greater decline in fractional shortening in males compared to females. Early proteomic profiling identified 5184 proteins and revealed widespread remodeling across metabolic, mitochondrial, cytoskeletal, and stress-response pathways. While doxorubicin induced broad proteomic changes in both sexes, two-way limma-based sex-stratified analyses identified 430 proteins exhibiting significant sex-by-treatment interactions. Our results suggested that doxorubicin was associated with alterations in oxidative phosphorylation, fatty acid metabolism, and calcium handling pathways. A female-specific upregulation of mitochondrial proteins, including Sco1, Cox17, and Atp2a2, which may be associated with preserved energetics and Ca handling, was detected. In contrast, male hearts demonstrated reduced Micu1 and RyR2 together with increased levels of Ppp1ca, findings that may indicate alterations in mitochondrial function and, excitation-contraction coupling. We also observed lower levels of calcineurin (Ppp3cb) in females. Baseline proteomic differences between sexes further implied distinct regulatory states that may shape the cardiac response to doxorubicin.Together, these findings suggest early proteomic remodeling upon doxorubicin treatment and represent candidate molecular targets that warrant functional validation in future studies. This work offers hypothesis-generating mechanistic insights into sex-specific responses to anthracycline-induced cardiomyopathy and underscores the importance of incorporating sex as a biological variable in cardio-oncology research. - Source: PubMed
Publication date: 2026/08/15
Sedighi SogolChen LijunWang YuefenLebarbenchon KauiYi JenaMenghani TanviShah Firasat AliYang SamSaeki HarumiIto TomoakiOrita HajimeZhang HuiO'Rourke BrianFoster D BrianGabrielson Kathleen L - The 5' mRNA leader regulates translation through its length and upstream open reading frames (uORFs), but its systematic remodeling in cancer remains unclear. We analyzed isoform-weighted 5' leader features across The Cancer Genome Atlas, the Genotype-Tissue Expression transcriptomes and the Clinical Proteomic Tumor Analysis Consortium proteogenomic cohorts. Tumor-associated shifts frequently opposed normal tissue aging trajectories, with the clearest signals in lung adenocarcinoma and lung squamous cell carcinoma. Raw closed-uORF burden defined the sharpest paired-supported lung cores, whereas residualized closed-uORF burden provided the most stable length-independent signal. Colon adenocarcinoma reproduced the transcriptomic pattern but showed a prominent adjacent-normal field effect, with nontumor colon already shifted toward the tumor pattern relative to healthy colon. Upstream-initiation features did not improve proteome-wide prediction beyond mRNA abundance but showed modest, gene-selective associations within independently prioritized age-opposed lung gene sets. Recurrent proteogenomic anchors included and . These findings define an age-opposed, tissue-dependent pattern of 5' leader remodeling and prioritize specific genes and isoforms for functional investigation. - Source: PubMed
Publication date: 2026/08/18
Pal AyonPal RanavRoy VivekChaki Madhumita GRoy Bhaskar - To report a rare case of refractory generalized Darier's disease (DD), also known as keratosis follicularis, with a disease duration exceeding 40 years and to explore the therapeutic effect of the interleukin-17A inhibitor secukinumab. - Source: PubMed
Publication date: 2026/08/13
Ou YangfeiFang HuiLiu TingtingCai ZongkunCheng Li - Congenital pathogenic gene variants may not elicit symptoms until later in life, highlighting the importance of identifying extra-genetic factors influencing the onset and severity of heritable diseases. We explored this in Darier disease (DD or -nEDD), an autosomal dominant skin disorder arising from heterozygous variants leading to haploinsufficiency of the endoplasmic reticulum (ER) calcium pump, SERCA2. Metabolic analysis of epidermal keratinocytes from confirmed patients with DD revealed abnormalities in the pentose phosphate pathway responsible for regenerating antioxidants like glutathione, accompanied by diminished free glutathione and increased glutathione-based, oxidative modifications of SERCA2. Induction of oxidative stress weakened intercellular adhesion, a defining characteristic of DD, which antioxidant treatment improved. Treatment with antioxidants or SERCA activators also diminished glutathionylation, consistent with SERCA2 haploinsufficiency giving rise to oxidative stress and placing residual SERCA2 at risk of oxidation. We posit that partial loss of protein activity primes cells for stress-induced loss of the remaining activity, a mechanism that may drive disease flares in other haploinsufficiencies. - Source: PubMed
Publication date: 2026/08/05
Harmon Robert MMcCarthy Erin FKrol AnnetteShetti AashutoshBraun JonasDiDominicis Rosemary JGodsel LisaRen ZiyouPerez White Bethany ECohen-Barak EranDodiuk-Gad RoniGudjonsson Johann EPaller Amy SSimpson Cory LWeinberg SamuelDahl RussellGoyal YogeshPrakriya MuraliGreen Kathleen J - In this case series, we report six patients with severe, treatment-refractory Darier disease, or dyskeratosis follicularis, also known as -nEDD (nonsyndromic epidermal differentiation disorder), treated with off-label biologic therapy, including dupilumab ( = 3), secukinumab followed by guselkumab ( = 1), and ustekinumab ( = 2). All patients had longstanding disease with recurrent flares, frequent infections and substantial impairment of quality of life, despite multiple conventional treatments. All biologic treatments were well tolerated, with no serious adverse events. Dupilumab consistently improved pruritus but had limited effects on skin lesions. Secukinumab and guselkumab provided only transient or partial disease control. In contrast, both patients treated with ustekinumab achieved pronounced and sustained clinical improvement, with markedly reduced disease severity and pruritus, and considerable improved quality of life. The pronounced and sustained responses observed with ustekinumab support its prioritization for future studies in Darier disease. - Source: PubMed
Publication date: 2026/06/23
Skarnvad Andersen AnnaBaez ElenaEmmanuel ThomasRønholt KirstenSommerlund MetteJohansen Claus