scholarly journals Targeted deletion of Ruvbl1 results in severe defects of epidermal development and perinatal mortality

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Claudia Dafinger ◽  
Thomas Benzing ◽  
Jörg Dötsch ◽  
Bernhard Schermer ◽  
Max C. Liebau
Keyword(s):  
Cell Death ◽  
Cellular Proliferation ◽  
Perinatal Death ◽  
Skin Barrier ◽  
Signaling Networks ◽  
Severe Phenotype ◽  
Targeted Deletion ◽  
Complex Process ◽  
Aaa Atpases ◽  
Epidermal Development

AbstractEpidermal development is a complex process of regulated cellular proliferation, differentiation, and tightly controlled cell death involving multiple cellular signaling networks. Here, we report a first description linking the AAA+ (ATPases associated with various cellular activities) superfamily protein Ruvbl1 to mammalian epidermal development. Keratinocyte-specific Ruvbl1 knockout mice (Ruvbl1fl/flK14:Cretg) show a severe phenotype including dramatic structural epidermal defects resulting in the loss of the functional skin barrier and perinatal death. Thus, Ruvbl1 is a newly identified essential player for the development of differentiated epidermis in mice.

scholarly journals Caspase-14—From Biomolecular Basics to Clinical Approach. A Review of Available Data

2021 ◽  
Vol 22 (11) ◽  
pp. 5575
Author(s):  
Agnieszka Markiewicz ◽  
Dawid Sigorski ◽  
Mateusz Markiewicz ◽  
Agnieszka Owczarczyk-Saczonek ◽  
Waldemar Placek
Keyword(s):  
Cell Death ◽  
Physiological Role ◽  
Skin Barrier ◽  
Clinical Aspects ◽  
Clinical Approach ◽  
Search Term ◽  
Caspase Family ◽  
Skin Conditions ◽  
Theoretical Science

Caspase-14 is a unique member of the caspase family—a family of molecules participating in apoptosis. However, it does not affect this process but regulates another form of programmed cell death—cornification, which is characteristic of the epidermis. Therefore, it plays a crucial role in the formation of the skin barrier. The cell death cycle has been a subject of interest for researchers for decades, so a lot of research has been done to expand the understanding of caspase-14, its role in cell homeostasis and processes affecting its expression and activation. Conversely, it is also an interesting target for clinical researchers searching for its role in the physiology of healthy individuals and its pathophysiology in particular diseases. A summary was done in 2008 by Denecker et al., concentrating mostly on the biotechnological aspects of the molecule and its physiological role. However, a lot of new data have been reported, and some more practical and clinical research has been conducted since then. The majority of studies tackled the issue of clinical data presenting the role of caspase in the etiopathology of many diseases such as retinal dysfunctions, multiple malignancies, and skin conditions. This review summarizes the available knowledge on the molecular and, more interestingly, the clinical aspects of caspase-14. It also presents how theoretical science may pave the way for medical research. Methods: The authors analyzed publications available on PubMed until 21 March 2021, using the search term “caspase 14”.

932 Targeting the 19S Proteasomal Subunit, Rpt4, in Colon Cancer Cells Induces Cell Death and Reduces Cellular Proliferation In Vitro and In Vivo

2013 ◽  
Vol 144 (5) ◽  
pp. S-166-S-167
Author(s):  
Karen Boland ◽  
Caoimhin Concannon ◽  
Niamh McCawley ◽  
Elaine W. Kay ◽  
Deborah McNamara ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cellular Proliferation ◽  
Colon Cancer Cells ◽  
Proliferation In Vitro

scholarly journals Differentiating life and death: An inflammatory affair

2018 ◽  
Author(s):  
Dustin Lane
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Death ◽  
Cell Differentiation ◽  
Programmed Cell Death ◽  
Signaling Networks ◽  
Inhibitors Of Apoptosis ◽  
Life And Death ◽  
Cell Death Signaling ◽  
Cycle Dependent

Programmed cell death signaling networks are frequently activated to coordinate the process of cell differentiation, and a variety of apoptotic events can mediate the process. This can include the ligation of death receptors, the activation of downstream caspases, and the induction of chromatin fragmentation, and all of these events can occur without downstream induction of death. Importantly, regulators of programmed cell death also have established roles in mediating differentiation. This review will provide an overview of apoptosis and its regulation by Inhibitors of Apoptosis (IAPs) and Bcl-2 family members. It will then outline the cross-talk between NF-ĸB and apoptotic signaling in the regulation of apoptosis before discussing the function of these regulators in the control of cell differentiation. It will end on a discussion of how a DNA damage-directed, cell cycle-dependent differentiation program may be controlled across multiple passages through cell cycle, and will assert that the failure to properly differentiate is the underlying cause of cancer.

Epigenetic Silencing of Tumor Suppressor lncRNA NKILA: Implication on NF-κB Signaling in Non-Hodgkin’s Lymphoma

2020 ◽  
Author(s):  
Min Yue Zhang ◽  
Ming Dan Deng ◽  
Lu Qian Wang ◽  
Rex K.H. Au-Yeung ◽  
Chor Sang Chim
Keyword(s):  
Dna Methylation ◽  
Cell Death ◽  
Tumor Suppressor ◽  
Hodgkin’S Lymphoma ◽  
Cellular Proliferation ◽  
Cell Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Promoter Dna Methylation ◽  
Promoter Dna

Abstract Background: NKILA, localized to 20q13.31, is a negative regulator of NF-κB signaling implicated in carcinogenesis. As a CpG island is embedded in the promoter region of NKILA, we hypothesized that NKILA is a tumor suppressor lncRNA reversibly silenced by promoter DNA methylation in non-Hodgkin’s lymphoma (NHL). Results: By pyrosequencing-verified methylation-specific PCR (MSP), NKILA was unmethylated in normal healthy controls, including 10 peripheral blood buffy coats and 11 normal tonsils tissue, but completely methylated in one (10%) NHL cell line SU-DHL-6. Among the lymphoma cell lines, by semi-quantitative RT-PCR, methylation of NKILA was inversely correlated with its expression. In the completely methylated SU-DHL-6 cells, hypomethylation treatment with 5-Aza-2'-deoxycytidine resulted in promoter demethylation and re-expression of NKILA transcript. In NHL primary samples (n=102), NKILA methylation was observed none of mantle cell lymphoma (MCL) cases, but in 29 (51.79%) diffuse large-B cell lymphoma (DLBCL) and 4 (20%) peripheral T-cell lymphoma (PTCL) cases, hence preferentially methylated in DLBCL than MCL (P < 0.0001) and PTCL (P = 0.007). Mechanistically, knockdown of NKILA resulted in promoting IkBα phosphorylation, which was associated with nucleus translocation of total p65 and phosphorylated p65 in SU-DHL-1 cells, hence constitutive NF-κB activation. Functionally, knock-down of NKILA in SU-DHL-1 cells led to decreased cell death and increased cellular proliferation, indicating a tumor suppressor role of NKILA in NHL cells. Conclusions: NKILA was a tumour suppressor lncRNA frequently hypermethylated in DLBCL. Promoter DNA methylation-mediated NKILA silencing led to increase of cellular proliferation and decrease of cell death via repression of NF-κB signaling in NHL cells.

scholarly journals A Cell’s Fate: An Overview of the Molecular Biology and Genetics of Apoptosis

2019 ◽  
Vol 20 (17) ◽  
pp. 4133 ◽  
Author(s):  
Giovanna C. Cavalcante ◽  
Ana Paula Schaan ◽  
Gleyce Fonseca Cabral ◽  
Mayara Natália Santana-da-Silva ◽  
Pablo Pinto ◽  
...  
Keyword(s):  
Cell Death ◽  
Molecular Biology ◽  
Internal Stress ◽  
Current Literature ◽  
Intrinsic Pathway ◽  
Whole Process ◽  
Regulated Cell Death ◽  
Complex Process ◽  
Key Players ◽  
Interactive Networks

Apoptosis is one of the main types of regulated cell death, a complex process that can be triggered by external or internal stimuli, which activate the extrinsic or the intrinsic pathway, respectively. Among various factors involved in apoptosis, several genes and their interactive networks are crucial regulators of the outcomes of each apoptotic phase. Furthermore, mitochondria are key players in determining the way by which cells will react to internal stress stimuli, thus being the main contributor of the intrinsic pathway, in addition to providing energy for the whole process. Other factors that have been reported as important players of this intricate molecular network are miRNAs, which regulate the genes involved in the apoptotic process. Imbalance in any of these mechanisms can lead to the development of several illnesses, hence, an overall understanding of these processes is essential for the comprehension of such situations. Although apoptosis has been widely studied, the current literature lacks an updated and more general overview on this subject. Therefore, here, we review and discuss the mechanisms of apoptosis, highlighting the roles of genes, miRNAs, and mitochondria involved in this type of cell death.

Molecular characterization of rabbit CPP32 and its function in vascular smooth muscle cell apoptosis

1998 ◽  
Vol 274 (4) ◽  
pp. H1132-H1140 ◽  
Author(s):  
He Wang ◽  
Joan A. Keiser
Keyword(s):  
Cell Death ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Dna Fragmentation ◽  
Cellular Proliferation ◽  
Apoptotic Cell ◽  
Fold Increase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Degenerate Primers ◽  
Conserved Sequence

Vascular remodeling in atherogenesis is marked not only by cellular proliferation and migration but is also impacted by apoptotic cell death. Extensive studies have focused on the signal transduction events leading to apoptosis. CPP32, a member of the caspase/interleukin-1β-converting enzyme (ICE) protease family, has emerged as a central player in several reports of apoptosis pathways. Vascular smooth muscle cells (SMC) undergo apoptosis after treatment with various stimuli, including nitric oxide (NO) donors, such as sodium nitroprusside (SNP, 0.1–1 mM). The aim of the present study was to evaluate the role of CPP32 in SNP-induced apoptosis of SMC. We isolated a rabbit CPP32 cDNA by using degenerate primers and polymerase chain reaction technique. The predicted protein encoded by this cDNA contains the conserved sequence (QACRG) necessary for covalent linkage to poly(ADP-ribose) polymerase (PARP) as well as the three amino acids responsible for substrate recognition and catalysis reported in other caspase members. Using a segment of this cDNA as a probe, we found no change of CPP32 mRNA in cultured arterial SMC before and after SNP treatment. We also measured the protease activity of CPP32 against a chromophore p-nitroaniline (pNA)-labeled substrate, DEVD-pNA. Our results showed a dose-dependent increase of CPP32 activity in SMC, with a maximal 10-fold increase after SNP treatment. Addition of a competitive CPP32 inhibitor, DEVD-CHO, produced a 50% reduction in maximal stimulation. Immunoblot analysis illustrated that SNP treatment induced proteolytic cleavage of CPP32 into its enzymatically active subunit p17 as well as the degradation of PARP into a 85-kDa fragment. We further demonstrated that incubation of cultured SMC with DEVD-CHO significantly reduced SNP-induced DNA fragmentation. DNA fragmentation analysis was carried out using several methods including a cell death detection enzyme-linked immunosorbent assay kit, in situ end labeling, and DNA electrophoresis in agarose gel. Our data indicate that CPP32 mRNA is constitutively expressed in rabbit SMC and activation of CPP32 protein has a pivotal role in SNP-induced SMC apoptosis.

scholarly journals Inhibition of NGF deprivation–induced death by low oxygen involves suppression of BIMEL and activation of HIF-1

2005 ◽  
Vol 168 (6) ◽  
pp. 911-920 ◽  
Author(s):  
Liang Xie ◽  
Randall S. Johnson ◽  
Robert S. Freeman
Keyword(s):  
Cell Death ◽  
Cytochrome C ◽  
Protective Effect ◽  
Sympathetic Neurons ◽  
Hypoxia Inducible Factor ◽  
Trophic Factor ◽  
Low Oxygen ◽  
Cytochrome C Release ◽  
Targeted Deletion ◽  
Trophic Factor Deprivation

Changes in O2 tension can significantly impact cell survival, yet the mechanisms underlying these effects are not well understood. Here, we report that maintaining sympathetic neurons under low O2 inhibits apoptosis caused by NGF deprivation. Low O2 exposure blocked cytochrome c release after NGF withdrawal, in part by suppressing the up-regulation of BIMEL. Forced BIMEL expression removed the block to cytochrome c release but did not prevent protection by low O2. Exposing neurons to low O2 also activated hypoxia-inducible factor (HIF) and expression of a stabilized form of HIF-1α (HIF-1αPP→AG) inhibited cell death in normoxic, NGF-deprived cells. Targeted deletion of HIF-1α partially suppressed the protective effect of low O2, whereas deletion of HIF-1α combined with forced BIMEL expression completely reversed the ability of low O2 to inhibit cell death. These data suggest a new model for how O2 tension can influence apoptotic events that underlie trophic factor deprivation–induced cell death.

scholarly journals Sequential Application of Anticancer Drugs Enhances Cell Death by Rewiring Apoptotic Signaling Networks

Cell ◽  
2012 ◽  
Vol 149 (4) ◽  
pp. 780-794 ◽  
Author(s):  
Michael J. Lee ◽  
Albert S. Ye ◽  
Alexandra K. Gardino ◽  
Anne Margriet Heijink ◽  
Peter K. Sorger ◽  
...  
Keyword(s):  
Cell Death ◽  
Anticancer Drugs ◽  
Signaling Networks ◽  
Apoptotic Signaling
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