Alphab-crystallin (CRYAB) is a small heat shock protein with a chaperoning activity that is present in the postnatal healthy human brain in oligodendrocytes and in a few astrocytes. The involvement of CRYAB in cell differentiation, proliferation, signaling, cytoskeletal assembly, and apoptosis in various model systems has suggested that it might also play a role in the developing human brain. We analyzed the distribution and the levels of this molecular chaperone in healthy and polygenetically compromised (Down syndrome [DS]) human telencephalon at midgestation. We demonstrate that CRYAB is expressed in a temporospatial pattern by numerous radial glial cells and some early oligodendrocyte progenitors, including dividing cells, as well as a few astroglial cells in both healthy and DS fetal brains. We also found abundant phosphorylation of CRYAB at Ser-59, which mediates its antiapoptotic and cytoskeletal functions. There was only marginal phosphorylation at Ser-45.In contrast to our earlier study in young DS subjects, upregulation of phosphorylated CRYAB occurred rarely in DS fetuses. The distribution, the timing of appearance, and the results of colocalization studies suggest that CRYAB assists in the biological processes associated with developmental remodeling/differentiation and proliferation of select subpopulations of progenitor cells in human fetal brain at midgestation.
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http://dx.doi.org/10.1097/NEN.0b013e3181e5f515 | DOI Listing |
Cell Rep
January 2025
Department of Medicine and Life Sciences, Universitat Pompeu Fabra, 08003 Barcelona, Spain; Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology, 08028 Barcelona, Spain. Electronic address:
The redox state of proteins is essential for their function and guarantees cell fitness. Peroxiredoxins protect cells against oxidative stress, maintain redox homeostasis, act as chaperones, and transmit hydrogen peroxide signals to redox regulators. Despite the profound structural and functional knowledge of peroxiredoxins action, information on how the different functions are concerted is still scarce.
View Article and Find Full Text PDFJ Transl Med
January 2025
Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, Jiangsu, China.
Background: The sustained activation of androgen receptor splice variant-7 (AR-V7) is a key factor in the resistance of castration-resistant prostate cancer (CRPC) to second-generation anti-androgens such as enzalutamide (ENZ). The AR/AR-V7 protein is regulated by the E3 ubiquitin ligase STUB1 and a complex involving HSP70, but the precise mechanism remains unclear.
Methods: High-throughput RNA sequencing was used to identify differentially expressed circular RNAs (circRNAs) in ENZ-resistant and control CRPC cells.
Nat Cell Biol
January 2025
Institute of Biochemistry and Molecular Biology, Faculty of Medicine, University of Bonn, Bonn, Germany.
Mitochondria have to import a large number of precursor proteins from the cytosol. Chaperones keep these proteins in a largely unfolded state and guide them to the mitochondrial import sites. Premature folding, mitochondrial stress and import defects can cause clogging of import sites and accumulation of non-imported precursors, representing a critical burden for cellular proteostasis.
View Article and Find Full Text PDFChem Biol Drug Des
January 2025
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Erzincan Binali Yildirim University, Erzincan, Turkiye.
Invasive fungal infections (IFIs) pose significant challenges in clinical settings, particularly due to their high morbidity and mortality rates. The rising incidence of these infections, coupled with increasing antifungal resistance, underscores the urgent need for novel therapeutic strategies. Current antifungal drugs target the fungal cell membrane, cell wall, or intracellular components, but resistance mechanisms such as altered drug-target interactions, enhanced efflux, and adaptive cellular responses have diminished their efficacy.
View Article and Find Full Text PDFJ Phys Chem B
January 2025
Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.
Intermolecular hydrogen bonds between carboxyl (COO) and amino groups are a common weak interaction in proteins. Infrared (IR) spectral assignment of such an intermolecular hydrogen bond provides a fingerprint for studying protein-protein interactions as its absorption frequency is affected by the molecular electrostatic environment. Temperature-dependent FTIR and temperature-jump time-resolved IR absorbance difference spectra of several typical amino acids and those of wild type and single-site mutated αB-crystallin were performed.
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