Identification of a novel heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) ligand that disrupts HnRNPA2B1/nucleic acid interactions to inhibit the MDMX-p53 axis in gastric cancer

Hu, Lei; Liu, Shuqi; Yao, Hongying; Hu, Yuemiao; Wang, Yingjie; Jiang, Jingpeng; Li, Xiaopeng; Fu, Fenghua; Yin, Qinye; Wang, Hongbo

doi:10.1016/j.phrs.2023.106696

Cited by 13 publications

(8 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…VEGFR2 was not detected in MDMX and PICALM IP, probably because of the limited binding capacity of the MDMX and PICALM antibody charged on the beads. Among the proteins that co-immunoprecipitated with MDMX were PICALM, annexins, arginase-1, RNA-binding protein HNPNPA2B1 [ 34 ] and others that immunoprecipitated also in VEGFR2 and PICALM IP (Supplementary Tables 1 , 3 ). Protein-glutamine gamma-glutamyltransferase 2 (TGM2) , which co-immunoprecipitated with MDMX and PICALM (Supplementary Tables 2 , 3 ), catalyzes protein cross-linking, is considered a bridge between inflammation and hypertension, and is upregulated in preeclampsia [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor

Ho,

Chaput,

Sinkey

et al. 2024

Cell Commun Signal

View full text Add to dashboard Cite

VEGFR2 (Vascular endothelial growth factor receptor 2) is a central regulator of placental angiogenesis. The study of the VEGFR2 proteome of chorionic villi at term revealed its partners MDMX (Double minute 4 protein) and PICALM (Phosphatidylinositol-binding clathrin assembly protein). Subsequently, the oxytocin receptor (OT-R) and vasopressin V1aR receptor were detected in MDMX and PICALM immunoprecipitations. Immunogold electron microscopy showed VEGFR2 on endothelial cell (EC) nuclei, mitochondria, and Hofbauer cells (HC), tissue-resident macrophages of the placenta. MDMX, PICALM, and V1aR were located on EC plasma membranes, nuclei, and HC nuclei. Unexpectedly, PICALM and OT-R were detected on EC projections into the fetal lumen and OT-R on 20–150 nm clusters therein, prompting the hypothesis that placental exosomes transport OT-R to the fetus and across the blood–brain barrier. Insights on gestational complications were gained by univariable and multivariable regression analyses associating preeclampsia with lower MDMX protein levels in membrane extracts of chorionic villi, and lower MDMX, PICALM, OT-R, and V1aR with spontaneous vaginal deliveries compared to cesarean deliveries before the onset of labor. We found select associations between higher MDMX, PICALM, OT-R protein levels and either gravidity, diabetes, BMI, maternal age, or neonatal weight, and correlations only between PICALM-OT-R (p < 2.7 × 10–8), PICALM-V1aR (p < 0.006), and OT-R-V1aR (p < 0.001). These results offer for exploration new partnerships in metabolic networks, tissue-resident immunity, and labor, notably for HC that predominantly express MDMX.

show abstract

Section: Resultsmentioning

confidence: 99%

Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor

Ho,

Chaput,

Sinkey

et al. 2024

Cell Commun Signal

View full text Add to dashboard Cite

show abstract

“…The LNCaP cells were harvested, washed, and suspended in PBS. Then 2×10 6 cells were injected subcutaneously into the right flank regions of the mice ( Hu et al, 2023 ). When the tumors reached an average volume of 100–300 mm 3 , the mice were randomized into five groups (n = 6/group): a) Control; b) 10 mg/kg Docetaxel; c) 50 mg/kg PCC0208057; d) 100 mg/kg PCC0208057.…”

Section: Methodsmentioning

confidence: 99%

PCC0208057 as a small molecule inhibitor of TRPC6 in the treatment of prostate cancer

Wei,

Li,

et al. 2024

Front. Pharmacol.

Self Cite

View full text Add to dashboard Cite

Prostate cancer (PCa) is a common malignant tumor, whose morbidity and mortality keep the top three in the male-related tumors in developed countries. Abnormal ion channels, such as transient receptor potential canonical 6 (TRPC6), are reported to be involved in the carcinogenesis and progress of prostate cancer and have become potential drug targets against prostate cancer. Here, we report a novel small molecule inhibitor of TRPC6, designated as PCC0208057, which can suppress the proliferation and migration of prostate cancer cells in vitro, and inhibit the formation of Human umbilical vein endothelial cells cell lumen. PCC0208057 can effectively inhibit the growth of xenograft tumor in vivo. Molecular mechanism studies revealed that PCC0208057 could directly bind and inhibit the activity of TRPC6, which then induces the prostate cancer cells arrested in G2/M phase via enhancing the phosphorylation of Nuclear Factor of Activated T Cells (NFAT) and Cdc2. Taken together, our study describes for the first time that PCC0208057, a novel TRPC6 inhibitor, might be a promising lead compound for treatment of prostate cancer.

show abstract

“…[174][175][176] MDMX and MDM2 belong to the E3 ubiquitin-ligase class and have a similar structure to MDM2. 177 MDMX only has the ability to bind and inhibit p53 but lacks the ability to induce the degradation of p53. However, MDMX can bind to MDM2 as a heterodimer to stabilize MDM2, which promotes the ubiquitination of p53 by MDM2.…”

Section: P53 Inactivation-related Factorsmentioning

confidence: 99%

“…MDMX and MDM2 belong to the E3 ubiquitin‐ligase class and have a similar structure to MDM2 177 . MDMX only has the ability to bind and inhibit p53 but lacks the ability to induce the degradation of p53.…”

Section: Activation and Inactivation Of P53mentioning

confidence: 99%

Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies

Shen¹,

Wang²,

Mao³

et al. 2023

MedComm

View full text Add to dashboard Cite

Tumor suppressor p53 can transcriptionally activate downstream genes in response to stress, and then regulate the cell cycle, DNA repair, metabolism, angiogenesis, apoptosis, and other biological responses. p53 has seven functional domains and 12 splice isoforms, and different domains and subtypes play different roles. The activation and inactivation of p53 are finely regulated and are associated with phosphorylation/acetylation modification and ubiquitination modification, respectively. Abnormal activation of p53 is closely related to the occurrence and development of cancer. While targeted therapy of the p53 signaling pathway is still in its early stages and only a few drugs or treatments have entered clinical trials, the development of new drugs and ongoing clinical trials are expected to lead to the widespread use of p53 signaling‐targeted therapy in cancer treatment in the future. TRIAP1 is a novel p53 downstream inhibitor of apoptosis. TRIAP1 is the homolog of yeast mitochondrial intermembrane protein MDM35, which can play a tumor‐promoting role by blocking the mitochondria‐dependent apoptosis pathway. This work provides a systematic overview of recent basic research and clinical progress in the p53 signaling pathway and proposes that TRIAP1 is an important therapeutic target downstream of p53 signaling.

show abstract

Identification of a novel heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) ligand that disrupts HnRNPA2B1/nucleic acid interactions to inhibit the MDMX-p53 axis in gastric cancer

Cited by 13 publications

References 43 publications

Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor

Proteomic studies of VEGFR2 in human placentas reveal protein associations with preeclampsia, diabetes, gravidity, and labor

PCC0208057 as a small molecule inhibitor of TRPC6 in the treatment of prostate cancer

Targeting the p53 signaling pathway in cancers: Molecular mechanisms and clinical studies

Contact Info

Product

Resources

About