B cell lymphoma 2 (Bcl-2) residues essential for Bcl-2's apoptosis-inducing interaction with Nur77/Nor-1 orphan steroid receptors

Banta, Karl L.; Wang, Xinyue; Das, Phani B.; Winoto, Astar

doi:10.1074/jbc.ra117.001101

Cited by 22 publications

(24 citation statements)

References 64 publications

(103 reference statements)

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“…In line with this, NOR-1/Nur77 mediated the apoptosis of immature thymocytes in response to T-cell antigen receptor signaling during T cell development [239,240]. Mitochondrial translocation of Nur factors and interaction with Bcl-2 were associated with a pro-apoptotic effect of NOR-1/Nur77 [241]. 6-mercaptopurine (6-MP), a widely used anti-neoplastic and anti-inflammatory drug, functions as an agonist of NOR-1 by activating its AF-1 domain [242].…”

Section: Neuron Derived Orphan Receptor 1 (Nor-1)supporting

confidence: 56%

Nuclear Receptors as Regulators of Pituitary Corticotroph Pro-Opiomelanocortin Transcription

Zhang

Heaney

2020

Cells

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The hypothalamic–pituitary–adrenal (HPA) axis plays a critical role in adaptive stress responses and maintaining organism homeostasis. The pituitary corticotroph is the central player in the HPA axis and is regulated by a plethora of hormonal and stress related factors that synergistically interact to activate and temper pro-opiomelanocortin (POMC) transcription, to either increase or decrease adrenocorticotropic hormone (ACTH) production and secretion as needed. Nuclear receptors are a family of highly conserved transcription factors that can also be induced by various physiologic signals, and they mediate their responses via multiple targets to regulate metabolism and homeostasis. In this review, we summarize the modulatory roles of nuclear receptors on pituitary corticotroph cell POMC transcription, describe the unique and complex role these factors play in hypothalamic–pituitary–adrenal axis (HPA) regulation and discuss potential therapeutic targets in disease states.

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Section: Neuron Derived Orphan Receptor 1 (Nor-1)supporting

confidence: 56%

Nuclear Receptors as Regulators of Pituitary Corticotroph Pro-Opiomelanocortin Transcription

Zhang

Heaney

2020

Cells

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“…Bcl-2 related X (Bax) is a homologous to Bcl-2 and an apoptosispromoting gene in the Bcl-2 gene family. [40][41][42] Overexpression of Bax can antagonize the protective effect of Bcl-2 and lead to cell death. Our results shown that Bcl-2 were down expression in miR-34a/CLMBs group and miR-34a/CLMBs and sPD-1/CLMBs mixed group.…”

Section: Discussionmentioning

confidence: 99%

<p>Ultrasound-Mediated Co-Delivery of miR-34a and sPD-1 Complexed with Microbubbles for Synergistic Cancer Therapy</p>

Qin

Tang

et al. 2020

CMAR

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Background: miR-34a was downregulated and PD-L1 was upregulated in cervical cancer; however, the treatment of cervical cancer lacks precision and targeting. This study explored the ultrasound-mediated co-delivery of miR-34a and sPD-1 complexes with microbubbles for synergistic cancer therapy. Methods: Cationic lipid microbubbles (CLMBs) were prepared by membrane hydration and mechanical oscillation. U14 subcutaneous xenograft mice were injected with CLMBs-loaded sPD-1 and miR-34a combined with ultrasound targeted destruction, and tumor volume and tumor weight of mice were measured. TUNEL apoptosis test and the mRNA expression of apoptosis-related gene Bcl-2 and Bax were analyzed by qRT-PCR. Antitumor immunerelated cytokines IFN-γ were investigated by qRT-PCR, LDH Cytotoxicity Assay Kit were performed to test cytotoxic T lymphocytes (CTL). Results: CLMBs were successfully prepared and the plasmid bound to its surface. The tumor volume and weight were specifically decreased by ultrasound-mediated co-delivery of miR-34a and sPD-1 complexes with microbubbles, apoptosis was induced and the apoptosis suppressor gene Bcl-2 was downregulated and proapoptotic gene Bax were upregulated. qRT-PCR analysis revealed that antitumor immunity-related IFN-γ was strongly upregulated in mice, which were treated with CLMBs-loaded sPD-1 and miR-34a combined with ultrasound targeted destruction, and the percentage of CTL was increased. Conclusion: These findings from the study demonstrated that CLMBs could deliver miR-34a and sPD-1, combined with ultrasound targeted destruction, could suppress the tumor tissue growing, induce apoptosis and enhance antitumor immunity in U14 subcutaneous xenograft mice.

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“…interferon inducible protein (AIM2) [67] • DNA-demethylating agents [68] • Drugs that targets IGF2 [69] • Neurotrophic tyrosine kinase (NTRK) [70] • Wnt/ -catenin pathway [71] Prostate • Androgen receptor splice variant 7 [72] • ROR- [73] • Mannose-6-phosphate [74] • Icaritin-activated arylhydrocarbon [75] Lymphoma blood cancer • Autologous T cells expressing CD30 chimeric antigen [79] • Interleukin (IL)-31 [80] • Anti-CD20, CD19 single chain fragment variable (SCFV)-based chimeric antigen [81] • Nur77/Nor-1 orphan steroid receptors [82] • Receptor-type tyrosine-protein phosphatase [83] • Chimeric antigen receptors (CAR) [84] • Interleukin10 [85] Myeloma and leukemia blood cancer…”

Section: Cancer Typementioning

confidence: 99%

Advancing Aptamers as Molecular Probes for Cancer Theranostic Applications—The Role of Molecular Dynamics Simulation

Jeevanandam

Tan

Danquah

et al. 2020

Biotechnology Journal

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Theranostics cover emerging technologies for cell biomarking for disease diagnosis and targeted introduction of drug ingredients to specific malignant sites. Theranostics development has become a significant biomedical research endeavor for effective diagnosis and treatment of diseases, especially cancer. An efficient biomarking and targeted delivery strategy for theranostic applications requires effective molecular coupling of binding ligands with high affinities to specific receptors on the cancer cell surface. Bioaffinity offers a unique mechanism to bind specific target and receptor molecules from a range of non‐targets. The binding efficacy depends on the specificity of the affinity ligand toward the target molecule even at low concentrations. Aptamers are fragments of genetic materials, peptides, or oligonucleotides which possess enhanced specificity in targeting desired cell surface receptor molecules. Aptamer–target binding results from several inter‐molecular interactions including hydrogen bond formation, aromatic stacking of flat moieties, hydrophobic interaction, electrostatic, and van der Waals interactions. Advancements in Systematic Evolution of Ligands by Exponential Enrichment (SELEX) assay has created the opportunity to artificially generate aptamers that specifically bind to desired cancer and tumor surface receptors with high affinities. This article discusses the potential application of molecular dynamics (MD) simulation to advance aptamer‐mediated receptor targeting in targeted cancer therapy. MD simulation offers real‐time analysis of the molecular drivers of the aptamer‐receptor binding and generate optimal receptor binding conditions for theranostic applications. The article also provides an overview of different cancer types with focus on receptor biomarking and targeted treatment approaches, conventional molecular probes, and aptamers that have been explored for cancer cells targeting.

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B cell lymphoma 2 (Bcl-2) residues essential for Bcl-2's apoptosis-inducing interaction with Nur77/Nor-1 orphan steroid receptors

Cited by 22 publications

References 64 publications

Nuclear Receptors as Regulators of Pituitary Corticotroph Pro-Opiomelanocortin Transcription

Nuclear Receptors as Regulators of Pituitary Corticotroph Pro-Opiomelanocortin Transcription

<p>Ultrasound-Mediated Co-Delivery of miR-34a and sPD-1 Complexed with Microbubbles for Synergistic Cancer Therapy</p>

Advancing Aptamers as Molecular Probes for Cancer Theranostic Applications—The Role of Molecular Dynamics Simulation

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