scholarly journals The selective continued linkage of centromeres from mitosis to interphase in the absence of mammalian separase

2006 ◽  
Vol 172 (6) ◽  
pp. 835-846 ◽  
Author(s):  
Kazuki Kumada ◽  
Ryoji Yao ◽  
Tokuichi Kawaguchi ◽  
Mika Karasawa ◽  
Yutaka Hoshikawa ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Centromeric Region ◽  
Cell Number ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Sister Chromatids ◽  
Evolutionarily Conserved ◽  
Essential Function ◽  
Normal Mitosis ◽  
Chromosome Decondensation

Separase is an evolutionarily conserved protease that is essential for chromosome segregation and cleaves cohesin Scc1/Rad21, which joins the sister chromatids together. Although mammalian separase also functions in chromosome segregation, our understanding of this process in mammals is still incomplete. We generated separase knockout mice, reporting an essential function for mammalian separase. Separase-deficient mouse embryonic fibroblasts exhibited severely restrained increases in cell number, polyploid chromosomes, and amplified centrosomes. Chromosome spreads demonstrated that multiple chromosomes connected to a centromeric region. Live observation demonstrated that the chromosomes of separase-deficient cells condensed, but failed to segregate, although subsequent cytokinesis and chromosome decondensation proceeded normally. These results establish that mammalian separase is essential for the separation of centromeres, but not of the arm regions of chromosomes. Other cell cycle events, such as mitotic exit, DNA replication, and centrosome duplication appear to occur normally. We also demonstrated that heterozygous separase-deficient cells exhibited severely restrained increases in cell number with apparently normal mitosis in the absence of securin, which is an inhibitory partner of separase.

The Polyphenolic Compound Curcumin Conjugation with an Alkyne Moiety in the Process of Autophagy

2018 ◽  
Vol 46 (03) ◽  
pp. 673-687 ◽  
Author(s):  
Peiyi Yan ◽  
Xin Sun ◽  
Xiaochen Chen ◽  
Yun Chen ◽  
Xiao Wang ◽  
...  
Keyword(s):  
Therapeutic Agent ◽  
Mammalian Target Of Rapamycin ◽  
Autophagic Flux ◽  
Cell Growth Inhibition ◽  
Polyphenolic Compound ◽  
Mouse Embryonic Fibroblasts ◽  
Curcumin Treatment ◽  
Embryonic Fibroblasts ◽  
Evolutionarily Conserved ◽  
Related Proteins

Curcumin is a hydrophobic polyphenol derived from turmeric: the rhizome of the herb Curcumalonga. Autophagy is an evolutionarily conserved process, in which cellular proteins and organelles are engulfed in autophagosome and then fuses with lysosome for degradation. Our previous study showed that Curcumin activates lysosome and induce autophagy through inhibition of AKT (protein kinase K, PKB)-mammalian target of rapamycin (mTOR) pathway. But whether Curucmin affects the fusion of autophagosome-lysosome is still not clear. Here, we used Curcumin-probe conjugation with an alkyne moiety to label mouse embryonic fibroblasts (MEFs) and found that Curcumin targets autophagy-related proteins, enhances autophagic flux and activates lysosome in cells. Moreover, Curcumin treatment promotes the fusion of autophasosome-lysosome in MEFs. Second, the enhanced fusion of autophagosome-lysosome is attributed to mTOR suppression. Third, blockage of the autophagosome-lysosome fusion leads to cell growth inhibition by Curcumin. Taken together, data from our study indicates the importance of the fusion of autophagosome-lysosome in Curcumin-induced autophagy, which may facilitate the development of Curcumin as a potential therapeutic agent for oxidative stress-related diseases.

scholarly journals A cryptic hydrophobic pocket in the polo-box domain of the polo-like kinase PLK1 regulates substrate recognition and mitotic chromosome segregation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Pooja Sharma ◽  
Robert Mahen ◽  
Maxim Rossmann ◽  
Jamie E. Stokes ◽  
Bryn Hardwick ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Mitotic Chromosome ◽  
Substrate Recognition ◽  
Genome Integrity ◽  
Mitotic Progression ◽  
New Approach ◽  
Molecule Inhibitor ◽  
Evolutionarily Conserved ◽  
Essential Function ◽  
Carboxyl Terminal

Abstract The human polo-like kinase PLK1 coordinates mitotic chromosome segregation by phosphorylating multiple chromatin- and kinetochore-binding proteins. How PLK1 activity is directed to specific substrates via phosphopeptide recognition by its carboxyl-terminal polo-box domain (PBD) is poorly understood. Here, we combine molecular, structural and chemical biology to identify a determinant for PLK1 substrate recognition that is essential for proper chromosome segregation. We show that mutations ablating an evolutionarily conserved, Tyr-lined pocket in human PLK1 PBD trigger cellular anomalies in mitotic progression and timing. Tyr pocket mutations selectively impair PLK1 binding to the kinetochore phosphoprotein substrate PBIP1, but not to the centrosomal substrate NEDD1. Through a structure-guided approach, we develop a small-molecule inhibitor, Polotyrin, which occupies the Tyr pocket. Polotyrin recapitulates the mitotic defects caused by mutations in the Tyr pocket, further evidencing its essential function, and exemplifying a new approach for selective PLK1 inhibition. Thus, our findings support a model wherein substrate discrimination via the Tyr pocket in the human PLK1 PBD regulates mitotic chromosome segregation to preserve genome integrity.

Apoptosis and development

2003 ◽  
Vol 39 ◽  
pp. 11-24 ◽  
Author(s):  
Justin V McCarthy
Keyword(s):  
Drosophila Melanogaster ◽  
Mammalian Cells ◽  
Cell Number ◽  
Model Organisms ◽  
Biological Processes ◽  
Nematode Caenorhabditis Elegans ◽  
Apoptotic Pathway ◽  
Genetic Pathways ◽  
Evolutionarily Conserved ◽  
Multicellular Organisms

Apoptosis is an evolutionarily conserved process used by multicellular organisms to developmentally regulate cell number or to eliminate cells that are potentially detrimental to the organism. The large diversity of regulators of apoptosis in mammalian cells and their numerous interactions complicate the analysis of their individual functions, particularly in development. The remarkable conservation of apoptotic mechanisms across species has allowed the genetic pathways of apoptosis determined in lower species, such as the nematode Caenorhabditis elegans and the fruitfly Drosophila melanogaster, to act as models for understanding the biology of apoptosis in mammalian cells. Though many components of the apoptotic pathway are conserved between species, the use of additional model organisms has revealed several important differences and supports the use of model organisms in deciphering complex biological processes such as apoptosis.

scholarly journals Regulation of c-Fos Gene Expression by NF-κB: A p65 Homodimer Binding Site in Mouse Embryonic Fibroblasts but Not Human HEK293 Cells

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e84062 ◽  
Author(s):  
Yu-Cheng Tu ◽  
Duen-Yi Huang ◽  
Shine-Gwo Shiah ◽  
Jang-Shiun Wang ◽  
Wan-Wan Lin
Keyword(s):  
Gene Expression ◽  
Binding Site ◽  
Hek293 Cells ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts

scholarly journals Introduction of Mouse Embryonic Fibroblasts into Early Embryos: From Confusion to Constructive Discussion. Comment on Savatier, P. Introduction of Mouse Embryonic Fibroblasts into Early Embryos Causes Reprogramming and (Con)fusion. Cells 2021, 10, 772

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1534
Author(s):  
Krystyna Żyżyńska-Galeńska ◽  
Jolanta Karasiewicz ◽  
Agnieszka Bernat
Keyword(s):  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Early Embryos ◽  
Constructive Discussion

We would like to address the issues raised by Pierre Savatier in “Introduction of Mouse Embryonic Fibroblasts into Early Embryos Causes Reprogramming and (Con)Fusion” [...]

616 Mouse Embryonic Fibroblasts Null for the KrüPpel-Like Factor 4 Alleles Are Genetically Unstable

2008 ◽  
Vol 134 (4) ◽  
pp. A-86
Author(s):  
Engda G. Hagos ◽  
Amr Ghaleb ◽  
W Brian Dalton ◽  
Jonathan P. Katz ◽  
Klaus H. Kaestner ◽  
...  
Keyword(s):  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts

scholarly journals Introduction of Mouse Embryonic Fibroblasts into Early Embryos Causes Reprogramming and (Con)fusion

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 772
Author(s):  
Pierre Savatier
Keyword(s):  
Somatic Cell ◽  
Cell Nuclei ◽  
Mouse Embryonic Fibroblasts ◽  
Embryonic Fibroblasts ◽  
Early Embryos

The reprogramming of somatic cell nuclei to achieve pluripotency is one of the most important biological discoveries of the last few decades [...]

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