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- Andersson, Linda, 1973, et al.
(författare)
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Deficiency in perilipin 5 reduces mitochondrial function and membrane depolarization in mouse hearts.
- 2017
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Ingår i: The international journal of biochemistry & cell biology. - : Elsevier BV. - 1878-5875 .- 1357-2725. ; 91:Pt A, s. 9-13
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Tidskriftsartikel (refereegranskat)abstract
- Myocardial triglycerides stored in lipid droplets are important in regulating the intracellular delivery of fatty acids for energy generation in mitochondria, for membrane biosynthesis, and as agonists for intracellular signaling. Previously, we showed that deficiency in the lipid droplet protein perilipin 5 (Plin5) markedly reduces triglyceride storage in cardiomyocytes and increases the flux of fatty acids into phospholipids. Here, we investigated whether Plin5 deficiency in cardiomyocytes alters mitochondrial function. We found that Plin5 deficiency reduced mitochondrial oxidative capacity. Furthermore, in mitochondria from Plin5((-/)(-)) hearts, the fatty acyl composition of phospholipids in mitochondrial membranes was altered and mitochondrial membrane depolarization was markedly compromised. These findings suggest that mitochondria isolated from hearts deficient in Plin5, have specific functional defects.
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| 2. |
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| 3. |
- Carranza, Pedro G., et al.
(författare)
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Specific histone modifications play critical roles in the control of encystation and antigenic variation in the early-branching eukaryote Giardia lamblia
- 2016
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Ingår i: International Journal of Biochemistry and Cell Biology. - : Elsevier BV. - 1357-2725 .- 1878-5875. ; 81, s. 32-43
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Tidskriftsartikel (refereegranskat)abstract
- During evolution, parasitic microorganisms have faced the challenges of adapting to different environments to colonize a variety of hosts. Giardia lamblia, a common cause of intestinal disease, has developed fascinating strategies to adapt both outside and inside its host's intestine, such as trophozoite differentiation into cyst and the switching of its major surface antigens. How gene expression is regulated during these adaptive processes remains undefined. Giardia lacks some typical eukaryotic features, like canonical transcription factors, linker histone H1, and complex promoter regions; suggesting that post transcriptional and translational control of gene expression is essential for parasite survival. However, epigenetic factors may also play critical roles at the transcriptional level. Here, we describe the most common post -translational histone modifications; characterize enzymes involved in these reactions, and analyze their association with the Giardia's differentiation processes. We present evidence that NAD(+)-dependent and NAD(+)-independent histone deacetylases regulate encystation; however, a unique NAD(+)-independent histone deacetylase modulate antigenic switching. The rates of acetylation of H4K8 and H4K16 are critical for encystation, whereas a decrease in acetylation of H4K8 and methylation of H3K9 occur preferentially during antigenic variation. These results show the complexity of the mechanisms regulating gene expression in this minimalistic protozoan parasite.
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| 4. |
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| 5. |
- Liu, Sijia, et al.
(författare)
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Regulation of the TGF-beta pathway by deubiquitinases in cancer
- 2016
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Ingår i: International Journal of Biochemistry and Cell Biology. - : Elsevier BV. - 1357-2725 .- 1878-5875. ; 76, s. 135-145
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Forskningsöversikt (refereegranskat)abstract
- The transforming growth factor-beta (TGF-beta) pathway regulates diverse cellular processes. It signals via serine/threonine kinase receptors and intracellular Smad and non-Smad effector proteins. In cancer cells, aberrant TGF-beta signalling can lead to loss of growth inhibition and an increase in invasion, epithelial-to-mesenchymal transition (EMT) and metastasis. Therapeutic targeting of the pro-oncogenic TGF-beta responses is currently being explored as a potential therapy against certain invasive and metastatic cancer types. The ubiquitin post-translational regulation system is emerging as a key regulatory mechanism for the control of TGF-beta pathway components. In this review, we focus on the role of deubiquitinases (DUBS), which counteract the activity of E3 ubiquitin ligases. We will discuss the mechanisms by which specific DUBs control Smad and non-Smad TGF-beta signalling routes, and how perturbation of the expression and function of DUBs contributes to misregulation of TGF-beta signalling in cancer.
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| 6. |
- Martins, Rodrigo Prado, et al.
(författare)
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A matter of maturity : the impact of pre-mRNA processing in gene expression and antigen presentation
- 2017
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Ingår i: International Journal of Biochemistry and Cell Biology. - : Elsevier BV. - 1357-2725 .- 1878-5875. ; 91, s. 203-211
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Forskningsöversikt (refereegranskat)abstract
- RNA processing plays a pivotal role in the diversification of high eukaryotes transcriptome and proteome. The expression of gene products controlling a variety of cellular and physiological processes depends largely on a complex maturation process undergone by pre-mRNAs to become translation-competent mRNAs. Here we review the different mechanisms involved in the pre-mRNA processing and disclose their impact in the gene regulation process in eukaryotic cells. We describe some viral strategies targeting pre-mRNA processing to control gene expression and host immune response and discuss their relevance as tools for a better understanding of cell biology. Finally, we highlight accumulating evidences toward the occurrence of a translation event coupled to mRNA biogenesis in the nuclear compartment and argue how this is relevant for the production of antigenic peptide substrates for the major histocompatibility complex class I pathway.
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| 7. |
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| 8. |
- Petanidis, Savvas, et al.
(författare)
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In vitro and ex vivo vanadium antitumor activity in (TGF-beta)-induced EMT. Synergistic activity with carboplatin and correlation with tumor metastasis in cancer patients
- 2016
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Ingår i: International Journal of Biochemistry and Cell Biology. - : Elsevier BV. - 1357-2725 .- 1878-5875. ; 74, s. 121-134
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Tidskriftsartikel (refereegranskat)abstract
- Epithelial to mesenchymal transition (EMT) plays a key role in tumor progression and metastasis as a crucial event for cancer cells to trigger the metastatic niche. Transforming growth factor-beta (TGF-beta) has been shown to play an important role as an EMT inducer in various stages of carcinogenesis. Previous reports had shown that antitumor vanadium inhibits the metastatic potential of tumor cells by reducing MMP-2 expression and inducing ROS-dependent apoptosis. However, the role of vanadium in (TGF-beta)-induced EMT remains unclear. In the present study, we report for the first time on the inhibitory effects of vanadium on (TGF-beta)-mediated EMT followed by down-regulation of ex vivo cancer stem cell markers. The results demonstrate blockage of (TGF-beta)-mediated EMT by vanadium and reduction in the mitochondrial potential of tumor cells linked to EMT and cancer metabolism. Furthermore, combination of vanadium and carboplatin (a) resulted in synergistic antitumor activity in ex vivo cell cultures, and (b) prompted G(0)/G(1) cell cycle arrest and sensitization of tumor cells to carboplatin-induced apoptosis. Overall, the findings highlight the multifaceted antitumor action of vanadium and its synergistic antitumor efficacy with current chemotherapy drugs, knowledge that could be valuable for targeting cancer cell metabolism and cancer stem cell-mediated metastasis in aggressive chemoresistant tumors.
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| 9. |
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| 10. |
- Sánchez-Hernández, Noemí, et al.
(författare)
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Targeting proteins to RNA transcription and processing sites within the nucleus
- 2017
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Ingår i: International Journal of Biochemistry and Cell Biology. - : Elsevier BV. - 1357-2725 .- 1878-5875. ; 91, s. 194-202
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Tidskriftsartikel (refereegranskat)abstract
- Studies of the spatial organization of the highly compartmentalized eukaryotic nucleus and dynamics of transcription and RNA processing within it are fundamental for fully understanding how gene expression is regulated in the cell. Although some progress has been made in deciphering the functional consequences of this complex network of interacting molecules in the context of nuclear organization, how proteins and RNA move in the nucleus and how the transcription and RNA processing machineries find their targets are important questions that remain largely unexplored. Here, we review major hallmarks and novel insights regarding the movement of RNA and proteins in the context of nuclear organization as well as the mechanisms by which the proteins involved in RNA processing localize to specific nuclear compartments.
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