1. elektronické vydání 1 online zdroj (144 stran)
Jediná kniha na trhu, která si troufá odhalit a podrobně vysvětlit kaskadérské techniky a finty. Autor Rudolf Bok je kromě účasti v mnoha zahraničních filmových produkcí také zapsán v Guinnessově knize rekordů - je dodnes držitelem světového rekordu za tento svůj 58,28 metrů dlouhý skok.
372 s. : il.
- Konspekt
- Ortopedie. Chirurgie. Oftalmologie
- NLK Obory
- chirurgie
- MeSH
- biomechanika MeSH
- biometrie MeSH
- lidé MeSH
- loketní kloub fyziologie MeSH
- paže MeSH
- svaly anatomie a histologie fyziologie MeSH
- Check Tag
- lidé MeSH
The Bcl-2 protein family comprises both pro- and antiapoptotic members that control the permeabilization of the mitochondrial outer membrane, a crucial step in the modulation of apoptosis. Recent research has demonstrated that the carboxyl-terminal transmembrane domain (TMD) of some Bcl-2 protein family members can modulate apoptosis; however, the transmembrane interactome of the antiapoptotic protein Mcl-1 remains largely unexplored. Here, we demonstrate that the Mcl-1 TMD forms homooligomers in the mitochondrial membrane, competes with full-length Mcl-1 protein with regards to its antiapoptotic function, and induces cell death in a Bok-dependent manner. While the Bok TMD oligomers locate preferentially to the endoplasmic reticulum (ER), heterooligomerization between the TMDs of Mcl-1 and Bok predominantly takes place at the mitochondrial membrane. Strikingly, the coexpression of Mcl-1 and Bok TMDs produces an increase in ER mitochondrial-associated membranes, suggesting an active role of Mcl-1 in the induced mitochondrial targeting of Bok. Finally, the introduction of Mcl-1 TMD somatic mutations detected in cancer patients alters the TMD interaction pattern to provide the Mcl-1 protein with enhanced antiapoptotic activity, thereby highlighting the clinical relevance of Mcl-1 TMD interactions.
- MeSH
- apoptóza fyziologie MeSH
- buněčná smrt fyziologie MeSH
- endoplazmatické retikulum metabolismus MeSH
- HeLa buňky MeSH
- lidé MeSH
- mitochondriální membrány metabolismus MeSH
- mitochondrie metabolismus MeSH
- protein MCL-1 metabolismus MeSH
- proteinové domény MeSH
- protoonkogenní proteiny c-bcl-2 metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
As the genomic region containing the Bcl-2-related ovarian killer (BOK) locus is frequently deleted in certain human cancers, BOK is hypothesized to have a tumor suppressor function. In the present study, we analyzed primary non-small-cell lung carcinoma (NSCLC) tumors and matched lung tissues from 102 surgically treated patients. We show that BOK protein levels are significantly downregulated in NSCLC tumors as compared to lung tissues (p < 0.001). In particular, we found BOK downregulation in NSCLC tumors of grades two (p = 0.004, n = 35) and three (p = 0.031, n = 39) as well as in tumors with metastases to hilar (pN1) (p = 0.047, n = 31) and mediastinal/subcarinal lymph nodes (pN2) (p = 0.021, n = 18) as opposed to grade one tumors (p = 0.688, n = 7) and tumors without lymph node metastases (p = 0.112, n = 51). Importantly, in lymph node-positive patients, BOK expression greater than the median value was associated with longer survival (p = 0.002, Mantel test). Using in vitro approaches, we provide evidence that BOK overexpression is inefficient in inducing apoptosis but that it inhibits TGFβ-induced migration and epithelial-to-mesenchymal transition (EMT) in lung adenocarcinoma-derived A549 cells. We have identified epigenetic mechanisms, in particular BOK promoter methylation, as an important means to silence BOK expression in NSCLC cells. Taken together, our data point toward a novel mechanism by which BOK acts as a tumor suppressor in NSCLC by inhibiting EMT. Consequently, the restoration of BOK levels in low-BOK-expressing tumors might favor the overall survival of NSCLC patients.
- MeSH
- adenokarcinom genetika metabolismus sekundární MeSH
- apoptóza * MeSH
- epitelo-mezenchymální tranzice MeSH
- lidé MeSH
- lymfatické metastázy MeSH
- míra přežití MeSH
- nádorové biomarkery genetika metabolismus MeSH
- nádorové buňky kultivované MeSH
- nádory plic genetika metabolismus patologie MeSH
- nemalobuněčný karcinom plic genetika metabolismus sekundární MeSH
- prognóza MeSH
- protoonkogenní proteiny c-bcl-2 genetika metabolismus MeSH
- spinocelulární karcinom genetika metabolismus sekundární MeSH
- staging nádorů MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
270 s. : il.
- Konspekt
- Ortopedie. Chirurgie. Oftalmologie
- NLK Obory
- chirurgie
