p97 is a homohexameric, toroidal machine that harnesses the energy of ATP binding and hydrolysis to effect structural reorganization of a diverse and primarily uncharacterized set of substrate proteins. This action has been linked to endoplasmic reticulum associated degradation (ERAD), homotypic membrane fusion, transcription factor control, cell cycle progression, DNA repair, and post-mitotic spindle disassembly. Exactly how these diverse processes use p97 is not fully understood, but it is clear that binding sites, primarily on the N- and C-domains of p97, facilitate this diversity by coordinating a growing collection of cofactors. These cofactors act at the levels of mechanism, sub-cellular localization, and substrate modification. Another unifying theme is the use of ubiquitylation. Both p97 and many of the associated cofactors have demonstrable ubiquitin-binding competence. The present review will discuss some of the current mechanistic studies and controversies and how these relate to cofactors as well as discussing potential therapeutic targeting of p97.
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http://dx.doi.org/10.1039/c0mb00176g | DOI Listing |
Sci Adv
January 2025
Simpson Querrey Institute for Epigenetics, Department of Biochemistry and Molecular Genetics Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
The stability of RNA polymerase II (Pol II) is tightly regulated during transcriptional elongation for proper control of gene expression. Our recent studies revealed that promoter-proximal Pol II is destabilized via the ubiquitin E3 ligase cullin 3 (CUL3) upon loss of transcription elongation factor SPT5. Here, we investigate how CUL3 recognizes chromatin-bound Pol II as a substrate.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Epstein-Barr virus (EBV) establishes persistent infection, causes infectious mononucleosis, is a major trigger for multiple sclerosis and contributes to multiple cancers. Yet, knowledge remains incomplete about how the virus remodels host B cells to support lytic replication. We previously identified that EBV lytic replication results in selective depletion of plasma membrane (PM) B cell receptor (BCR) complexes, composed of immunoglobulin and the CD79A and CD79B signaling chains.
View Article and Find Full Text PDFFront Physiol
January 2025
Faculty of Physical Culture Sciences, Collegium Medicum im. dr. Władysława Biegańskiego, Jan Długosz University in Częstochowa, Częstochowa, Poland.
Introduction: This study aimed to assess the development of speed, endurance and power in young football players and to create percentile charts and tables for standardized assessment.
Methods: Cross-sectional data were collected from 495 male players aged 12-16 years at RKS Raków Częstochowa Academy in 2018-2022. Players participated in a systematic training in which running time 5 m, 10 m, 30 m, lower limb power (standing long jump), and Maximum Aerobic Speed (MAS) were measured using the 30-15 Intermittent Fitness Test.
Int J Mol Sci
December 2024
Department of Biology, Texas Southern University, Houston, TX 77004, USA.
Previous data show that the knockdown of the gene in the MDA-MB-231 cell line leads to the downregulation of gene expression. In addition, and genes are co-expressed and dysregulated in some of the same triple negative breast cancer patient samples. We propose that the co-expression of the two genes is attributed to the MYBL1 transcription factor regulation of the gene.
View Article and Find Full Text PDFMol Biol Cell
January 2025
Dept. of Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198.
The primary cilium is a crucial signaling organelle that can be generated by most human cells, and impediments to primary ciliogenesis lead to a variety of developmental disorders known as ciliopathies. The removal of the capping protein, CP110, from the mother centriole is a crucial early step that promotes generation of the ciliary vesicle and ciliogenesis. Recent studies have demonstrated that CP110 undergoes polyubiquitination and degradation in the proteosome, but the mechanisms of unfolding and removal from the mother centriole remain unknown.
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