Promyelocytic leukaemia (PML) nuclear bodies are present in most mammalian cell nuclei. PML bodies are disrupted by PML retinoic acid receptor alpha (RAR alpha) oncoproteins in acute promyelocytic leukaemia. These bodies contain numerous proteins, including Sp100, SUMO-1, HAUSP(USP7), CBP and BLM, and they have been implicated in aspects of transcriptional regulation or as nuclear storage depots. Here, we show that three classes of PML nuclear bodies can be distinguished, on the basis of their dynamic properties in living cells. One class of PML bodies is particularly noteworthy in that it moves by a metabolic-energy-dependent mechanism. This represents the first example of metabolic-energy-dependent transport of a nuclear body within the mammalian cell nucleus.
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http://dx.doi.org/10.1038/ncb740 | DOI Listing |
PLoS Pathog
January 2025
Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
IKKε is a traditional antiviral kinase known for positively regulating the production of type I interferon (IFN) and the expression of IFN-stimulated genes (ISGs) during various virus infections. However, through an inhibitor screen targeting cellular kinases, we found that IKKε plays a crucial role in the lytic replication of Kaposi's sarcoma-associated herpesvirus (KSHV). Mechanistically, during KSHV lytic replication, IKKε undergoes significant SUMOylation at both Lys321 and Lys549 by the viral SUMO E3 ligase ORF45.
View Article and Find Full Text PDFMedicine (Baltimore)
November 2024
Clinical laboratory, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China.
This study analyzes the laboratory characteristics and prognosis of patients between PML-RARα negative APL and PML-RARα positive APL and compares the differences in order to improve the understanding of this rare APL and guide clinical diagnosis and treatment. A total of 81 patients with newly diagnosed APL based on bone marrow cell morphology were included, with 14 in the PML-RARα gene negative group and 67 in the PML-RARα gene positive group. The sex, age, peripheral blood routine test, coagulation related indicators, bone marrow cell morphology, flow cytometric immunophenotype, abnormal chromosome expression and prognosis of the 2 groups were analyzed and compared.
View Article and Find Full Text PDFCytopathology
January 2025
Department of Pathology and Applied Neurobiology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
This is the first case report describing the diagnostic value of dot-shaped inclusions associated with promyelocytic leukaemia nuclear bodies (PML-NBs) to define JC virus-infected glial cells in an intraoperative cytopathological diagnosis for progressive multifocal leukoencephalopathy (PML).
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Département de Biologie, Université de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada.
To achieve replicative immortality, cancer cells must activate telomere maintenance mechanisms. In 10 to 15% of cancers, this is enabled by recombination-based alternative lengthening of telomeres pathways (ALT). ALT cells display several hallmarks including heterogeneous telomere length, extrachromosomal telomeric repeats, and ALT-associated PML bodies.
View Article and Find Full Text PDFCells
December 2024
Institute of Cytology of the Russian Academy of Sciences, Tikhoretsky av.4, 194064 St. Petersburg, Russia.
Natural aging and age-related diseases involve the acceleration of replicative aging, or senescence. Multiple proteins are known to participate in these processes, including the promyelocytic leukemia (PML) protein, which serves as a core component of nuclear-membrane-less organelles known as PML nuclear bodies (PML-NBs). In this work, morphological changes in PML-NBs and alterations in PML protein localization at the transition of primary fibroblasts to a replicative senescent state were studied by immunofluorescence.
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