AI Article Synopsis
Article Abstract
Constitutive androstane receptor (CAR) induces xenobiotic, bilirubin, and thyroid hormone metabolism as a heterodimer with the retinoid X receptor (RXR). Unlike ligand-dependent nuclear receptors, CAR is constitutively active. Here, we report the heterodimeric structure of the CAR and RXR ligand binding domains (LBDs), which reveals an unusually large dimerization interface and a small CAR ligand binding pocket. Constitutive CAR activity appears to be mediated by the compact nature of the CAR LBD that displays several unique features including a shortened AF2 helix and helix H10, which are linked by a two-turn helix that normally adopts an extended loop in other receptors, and an extended helix H2 that stabilizes the canonical LBD fold by packing tightly against helix H3. These structural observations provide a molecular framework for understanding the atypical transcriptional activation properties of CAR.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.molcel.2004.11.036 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Population Pharmacokinetics of Orvacabtagene Autoleucel, an Autologous BCMA-Directed Chimeric Antigen Receptor T-Cell Product, in Patients with Relapsed/Refractory Multiple Myeloma.
Clin Cancer Res
January 2025
Bristol-Myers Squibb (United States), Summit, New Jersey, United States.
Purpose: Orvacabtagene autoleucel (orva-cel; JCARH125), a CAR T-cell therapy targeting B-cell maturation antigen (BCMA), was evaluated in relapsed/refractory multiple myeloma (RRMM) patients in the EVOLVE phase 1/2 study (NCT03430011). We applied a modified piecewise model to characterize orva-cel transgene kinetics and assessed the impact of various covariates on its pharmacokinetics (PK).
Experimental Design: The population PK analysis included 159 patients from the EVOLVE study.
Cardiotoxic Effects Following CAR-T Cell Therapy: A Literature Review.
Curr Oncol Rep
January 2025
Department of Radiology, Albert Einstein College of Medicine and the Montefiore Medical Center, 111 East 210Th Street, Bronx, NY, 10461, USA.
Purpose Of Review: This paper reviewed the current literature on incidence, clinical manifestations, and risk factors of Chimeric Antigen Receptor T-cell (CAR-T) cardiotoxicity.
Recent Findings: CAR-T therapy has emerged as a groundbreaking treatment for hematological malignancies since FDA approval in 2017. CAR-T therapy is however associated with a few side effects, among which cardiotoxicity is of significant concern.
Advances in CAR T cell therapy: antigen selection, modifications, and current trials for solid tumors.
Front Immunol
January 2025
Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States.
Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of hematologic malignancies, achieving remarkable clinical success with FDA-approved therapies targeting CD19 and BCMA. However, the extension of these successes to solid tumors remains limited due to several intrinsic challenges, including antigen heterogeneity and immunosuppressive tumor microenvironments. In this review, we provide a comprehensive overview of recent advances in CAR T cell therapy aimed at overcoming these obstacles.
View Article and Find Full Text PDFUnlocking the Potential of CAR-NK Cell Therapy: Overcoming Barriers and Challenges in the Treatment of Myeloid Malignancies.
Mol Cancer Ther
January 2025
Tongji Hospital, Wuhan, Hubei, China.
Myeloid malignancies include various types of cancers that arise from abnormal development or proliferation of myeloid cells within the bone marrow. Chimeric antigen receptor (CAR) T cell treatments, which show great potential for B cell and plasma cell cancers, face major challenges when used for myeloid malignancies. CAR natural killer (NK) cell-based immunotherapy encounters several challenges in treating myeloid cancers, including: (1) poor gene transfer efficiency and expansion platforms in vitro, (2) limited proliferation and persistence in vivo, (3) antigenic heterogeneity, and (4) an immunosuppressive tumor microenvironment.
View Article and Find Full Text PDFManagement of chimeric antigen receptor T-cell-related toxicity of a patient affected by cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, followed by an intestinal perforation: a case report.
J Med Case Rep
January 2025
Director of Hospital Pharmacy, Santa Croce e Carle Hospital, Cuneo, Italy.
Background: Mantle cell lymphoma is a diverse B-cell lymphoma with varying clinical behaviors. Treating relapsed or refractory mantle cell lymphoma is challenging, with Bruton's tyrosine kinase inhibitors proving effective but not curative. Post-Bruton's tyrosine kinase inhibitor failure, the prognosis remains unfavorable.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!