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CUL4-Based Ubiquitin Ligases in Chromatin Regulation: An Evolutionary Perspective.
Cells
January 2025
Division of Cell Proliferation, United Centers for Advanced Research and Translational Medicine, Graduate School of Medicine, Tohoku University, Sendai 980-8575, Japan.
Ubiquitylation is a post-translational modification that modulates protein function and stability. It is orchestrated by the concerted action of three types of enzymes, with substrate specificity governed by ubiquitin ligases (E3s), which may exist as single proteins or as part of multi-protein complexes. Although Cullin (CUL) proteins lack intrinsic enzymatic activity, they participate in the formation of active ubiquitin ligase complexes, known as Cullin-Ring ubiquitin Ligases (CRLs), through their association with ROC1 or ROC2, along with substrate adaptor and receptor proteins.
View Article and Find Full Text PDFSymmetry facilitated the evolution of heterospecificity and high-order stoichiometry in vertebrate hemoglobin.
Proc Natl Acad Sci U S A
January 2025
Department of Ecology and Evolution, University of Chicago, Chicago, IL 60637.
Many proteins form paralogous multimers-molecular complexes in which evolutionarily related proteins are arranged into specific quaternary structures. Little is known about the mechanisms by which they acquired their stoichiometry (the number of total subunits in the complex) and heterospecificity (the preference of subunits for their paralogs rather than other copies of the same protein). Here, we use ancestral protein reconstruction and biochemical experiments to study historical increases in stoichiometry and specificity during the evolution of vertebrate hemoglobin (Hb), an αβ heterotetramer that evolved from a homodimeric ancestor after a gene duplication.
View Article and Find Full Text PDFEvolutionarily Developed Alternatively Spliced Exons Containing Translation Initiation Sites.
Cells
December 2024
Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-8550, Japan.
Alternative splicing is essential for the generation of various protein isoforms that are involved in cell differentiation and tissue development. In addition to internal coding exons, alternative splicing affects the exons with translation initiation codons; however, little is known about these exons. Here, we performed a systematic classification of human alternative exons using coding information.
View Article and Find Full Text PDFFine-Tuned Expression of Evolutionarily Conserved Signaling Molecules in the Notochord.
Int J Mol Sci
December 2024
Department of Molecular Pathobiology, New York University College of Dentistry, 345 E 24th Street, New York, NY 10010, USA.
The notochord is an axial structure required for the development of all chordate embryos, from sea squirts to humans. Over the course of more than half a billion years of chordate evolution, in addition to its structural function, the notochord has acquired increasingly relevant patterning roles for its surrounding tissues. This process has involved the co-option of signaling pathways and the acquisition of novel molecular mechanisms responsible for the precise timing and modalities of their deployment.
View Article and Find Full Text PDFHuman asthenozoospermia: Update on genetic causes, patient management, and clinical strategies.
Andrology
January 2025
Institute for Advanced Biosciences, INSERM U 1209, CNRS UMR 5309, Université Grenoble Alpes, Team "Physiopathology and Pathophysiology of Sperm Cells", Grenoble, France.
Background: In mammals, sperm fertilization potential relies on efficient progression within the female genital tract to reach and fertilize the oocyte. This fundamental property is supported by the flagellum, an evolutionarily conserved organelle, which contains dynein motor proteins that provide the mechanical force for sperm propulsion and motility. Primary motility of the sperm cells is acquired during their transit through the epididymis and hyperactivated motility is acquired throughout the journey in the female genital tract by a process called capacitation.
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