Chromatin-remodeling enzymes play essential roles in many biological processes, including gene expression, DNA replication and repair, and cell division. Although one such complex, SWI/SNF, has been extensively studied, new discoveries are still being made. Here, we review SWI/SNF biochemistry; highlight recent genomic and proteomic advances; and address the role of SWI/SNF in human diseases, including cancer and viral infections. These studies have greatly increased our understanding of complex nuclear processes.
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http://dx.doi.org/10.1074/jbc.R111.309302 | DOI Listing |
Mod Pathol
January 2025
Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL. Electronic address:
Deep penetrating nevi (DPNs) are characterized by activating mutations in the MAP kinase and Wnt/beta-catenin pathways that result in large melanocytes with increased nuclear atypia, cytoplasmic pigmentation, and often mitotic activity. Together with a lack of maturation, this constellation of findings creates challenges for pathologists to distinguish deep penetrating nevus (DPN) from DPN-like melanoma. To assess the utility of next generation sequencing (NGS) in resolving this diagnostic dilemma, we performed NGS studies on 35 lesions including 24 DPNs and 11 DPN-like melanomas to characterize the specific genomic differences between the two groups and elucidate the genetic events involved in malignant transformation of DPNs.
View Article and Find Full Text PDFEur J Cancer
November 2024
David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Purpose: MAK683, a first-in-class and highly selective allosteric inhibitor of the embryonic ectoderm development subunit of polycomb repressive complex 2, has shown sustained antitumor activity in tumor xenograft models. This first-in-human phase 1/2 study evaluated the safety, pharmacokinetics (PK), and clinical activity of single-agent MAK683 in advanced malignancies.
Methods: MAK683 was administered fasted once daily or twice daily continuously in 28-day treatment cycles.
J Cell Mol Med
January 2025
Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.
Bladder cancer originates from bladder tissues and is the ninth most common type of cancer worldwide. The SWI/SNF (SWItch/sucrose non- fermentable) complex plays a crucial role in regulating various biological processes, such as cell cycle control, DNA damage repair and transcription regulation. The purpose of this article is to examine the functional studies of the SWI/SNF complex in bladder cancer, highlighting new pathways for creating personalised treatment approaches for bladder cancer patients with mutations in the SWI/SNF complex.
View Article and Find Full Text PDFThe ARID1A gene, frequently mutated in cancer, encodes the AT-rich interactive domain-containing protein 1A, a key component of the chromatin remodeling SWI/SNF complex. The ARID1A protein features a conserved DNA-binding domain (ARID domain) of approximately 100 residues crucial for its function. Despite the frequency of mutations, the impact on ARID1A's stability and contribution to cancer progression remains unclear.
View Article and Find Full Text PDFBackground: Atypical teratoid rhabdoid tumor (ATRT) is the most common malignant brain tumor in infants, and more than 60% of children with ATRT die from their tumor. ATRT is associated with mutational inactivation/deletion of , a member of the SWI/SNF chromatin remodeling complex, suggesting that epigenetic events play a critical role in tumor development and progression. Moreover, disruption of SWI/SNF allows unopposed activity of epigenetic repressors, which contribute to tumorigenicity.
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