scholarly journals FAIM: An Antagonist of Fas-Killing and Beyond

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 541 ◽  
Author(s):  
Jianxin Huo ◽  
Shengli Xu ◽  
Kong-Peng Lam
Keyword(s):  
Molecular Mechanisms ◽  
Cell Receptor ◽  
Primary Role ◽  
The Past ◽  
Pathological Conditions ◽  
Apoptotic Protein ◽  
Evolutionarily Conserved ◽  
Inhibitory Molecule ◽  
Alternatively Spliced ◽  
Fas Apoptosis Inhibitory Molecule

Fas Apoptosis Inhibitory Molecule (FAIM) is an anti-apoptotic protein that is up-regulated in B cell receptor (BCR)-activated B cells and confers upon them resistance to Fas-mediated cell death. Faim has two alternatively spliced isoforms, with the short isoform ubiquitously expressed in various tissues and the long isoform mainly found in the nervous tissues. FAIM is evolutionarily conserved but does not share any significant primary sequence homology with any known protein. The function of FAIM has been extensively studied in the past 20 years, with its primary role being ascribed to be anti-apoptotic. In addition, several other functions of FAIM were also discovered in different physiological and pathological conditions, such as cell growth, metabolism, Alzheimer’s disease and tumorigenesis. However, the detailed molecular mechanisms underlying FAIM’s role in these conditions remain unknown. In this review, we summarize comprehensively the functions of FAIM in these different contexts and discuss its potential as a diagnostic, prognostic or therapeutic target.

scholarly journals MicroRNAs : An Emerging Player In Autophagy

2014 ◽  
Author(s):  
yongfei yang ◽  
CHENGYU LIANG
Keyword(s):  
Regulatory Network ◽  
Molecular Mechanisms ◽  
Regulation Of Gene Expression ◽  
Substantial Effect ◽  
Digestion Process ◽  
The Past ◽  
Pathological Conditions ◽  
Cellular Autophagy ◽  
Evolutionarily Conserved ◽  
Post Transcriptional Regulation

Autophagy is an evolutionarily conserved self-digestion process for the quality control of intracellular entities in eukaryotes. In the past few years, mounting evidence indicates that microRNAs (miRNAs)-mediated post-transcriptional regulation of gene expression represents an integral part of the autophagy regulatory network and may have a substantial effect on autophagy-related physiological and pathological conditions including cancer. Herein, we examine some of the molecular mechanisms by which microRNAs manipulate the autophagic machinery to maintain cellular homeostasis and their biological outputs during cancer development. A better understanding of interaction between microRNAs and cellular autophagy may ultimately benefit future cancer diagnostic and anticancer therapeutics.

Structure determination of human Fas apoptosis inhibitory molecule and identification of the critical residues linking the interdomain interaction to the anti-apoptotic activity

2014 ◽  
Vol 70 (7) ◽  
pp. 1812-1822 ◽  
Author(s):  
Guoming Li ◽  
Linglong Qu ◽  
Shuaipeng Ma ◽  
Yujie Wu ◽  
Changwen Jin ◽  
...  
Keyword(s):  
Solution Structure ◽  
Molecular Mechanisms ◽  
Terminal Domain ◽  
Apoptotic Protein ◽  
Inhibitory Molecule ◽  
Interdomain Interaction ◽  
Critical Residues ◽  
Fas Apoptosis Inhibitory Molecule ◽  
Biochemical Analyses ◽  
Apoptotic Activity

Fas apoptosis inhibitory molecule (FAIM) is a highly conserved anti-apoptotic protein which plays important roles in cells. There are two isoforms of FAIM, of which the short isoform FAIM-S is broadly expressed in all tissues, whereas the long isoform FAIM-L is exclusively expressed in the nervous system. No structure of human FAIM has been reported to date and the detailed molecular mechanisms underlying the anti-apoptotic function of FAIM remain unknown. Here, the crystal structure of the human FAIM-S N-terminal domain (NTD) and the NMR solution structure of the human FAIM-S C-terminal domain (CTD) were determined. The structures revealed that the NTD and CTD adopt a similar protein fold containing eight antiparallel β-strands which form two sheets. Both structural and biochemical analyses implied that the NTD exists as a dimer and the CTD as a monomer and that they can interact with each other. Several critical residues were identified to be involved in this interaction. Moreover, mutations of these critical residues also interfered in the anti-apoptotic activity of FAIM-S. Thus, the structural and functional data presented here will provide insight into the anti-apoptotic mechanism of FAIM-S.

scholarly journals The gut in iron homeostasis: role of HIF-2 under normal and pathological conditions

Blood ◽  
2013 ◽  
Vol 122 (6) ◽  
pp. 885-892 ◽  
Author(s):  
Maria Mastrogiannaki ◽  
Pavle Matak ◽  
Carole Peyssonnaux
Keyword(s):  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Iron Absorption ◽  
Hypoxia Inducible Factor ◽  
Therapeutic Strategies ◽  
The Past ◽  
Pathological Conditions ◽  
Per Se ◽  
Key Genes

Abstract Although earlier, seminal studies demonstrated that the gut per se has the intrinsic ability to regulate the rates of iron absorption, the spotlight in the past decade has been placed on the systemic regulation of iron homeostasis by the hepatic hormone hepcidin and the molecular mechanisms that regulate its expression. Recently, however, attention has returned to the gut based on the finding that hypoxia inducible factor-2 (HIF-2α) regulates the expression of key genes that contribute to iron absorption. Here we review the current understanding of the molecular mechanisms that regulate iron homeostasis in the gut by focusing on the role of HIF-2 under physiological steady-state conditions and in the pathogenesis of iron-related diseases. We also discuss implications for adapting HIF-2–based therapeutic strategies in iron-related pathological conditions.

scholarly journals Regulation of Nuclear Factor-kappaB Function by O-GlcNAcylation in Inflammation and Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Angela Rose Liu ◽  
Parameswaran Ramakrishnan
Keyword(s):  
Cell Proliferation ◽  
Posttranslational Modifications ◽  
Nuclear Factor Kappab ◽  
Nuclear Factor ◽  
Cancer Cell Proliferation ◽  
The Past ◽  
Pathological Conditions ◽  
Evolutionarily Conserved ◽  
Made In

Nuclear factor-kappaB (NF-κB) is a pleiotropic, evolutionarily conserved transcription factor family that plays a central role in regulating immune responses, inflammation, cell survival, and apoptosis. Great strides have been made in the past three decades to understand the role of NF-κB in physiological and pathological conditions. Carcinogenesis is associated with constitutive activation of NF-κB that promotes tumor cell proliferation, angiogenesis, and apoptosis evasion. NF-κB is ubiquitously expressed, however, its activity is under tight regulation by inhibitors of the pathway and through multiple posttranslational modifications. O-GlcNAcylation is a dynamic posttranslational modification that controls NF-κB-dependent transactivation. O-GlcNAcylation acts as a nutrient-dependent rheostat of cellular signaling. Increased uptake of glucose and glutamine by cancer cells enhances NF-κB O-GlcNAcylation. Growing evidence indicates that O-GlcNAcylation of NF-κB is a key molecular mechanism that regulates cancer cell proliferation, survival and metastasis and acts as link between inflammation and cancer. In this review, we are attempting to summarize the current understanding of the cohesive role of NF-κB O-GlcNAcylation in inflammation and cancer.

Management of prolymphocytic leukemia

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 361-367 ◽  
Author(s):  
Claire Dearden
Keyword(s):  
B Cell ◽  
Molecular Mechanisms ◽  
Cell Receptor ◽  
Underlying Disease ◽  
Current Therapy ◽  
Allogenic Stem Cell Transplantation ◽  
Prolymphocytic Leukemia ◽  
The Past ◽  
First Line Therapy ◽  
Purine Analog

B-cell (B-PLL) and T-cell (T-PLL) prolymphocytic leukemias are rare, poor-prognosis lymphoid neoplasms with similar presentation characterized by symptomatic splenomegaly and lymphocytosis. They can be distinguished from each other and from other T- and B-cell leukemias by careful evaluation of morphology, immunophenotyping, and molecular genetics. The clinical behavior is typically aggressive, although a subset of patients may have an indolent phase of variable length. First-line therapy for T-PLL is with intravenous alemtuzumab and for B-PLL is with combination purine analog-based chemo-immunotherapy. New B-cell receptor inhibitors, such as ibrutinib and idelalisib, may have a role in the management of B-PLL, especially for the patients harboring abnormalities of TP53. Allogenic stem cell transplantation should still be considered for eligible patients and may be the only current therapy capable of delivering a cure. In the past few years, many of the molecular mechanisms underlying disease pathogenesis and progression have been revealed and are likely to lead to the development of novel targeted approaches.

scholarly journals Management of prolymphocytic leukemia

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 361-367 ◽  
Author(s):  
Claire Dearden
Keyword(s):  
B Cell ◽  
Molecular Mechanisms ◽  
Cell Receptor ◽  
Underlying Disease ◽  
Current Therapy ◽  
Allogenic Stem Cell Transplantation ◽  
Prolymphocytic Leukemia ◽  
The Past ◽  
First Line Therapy ◽  
Purine Analog

Abstract B-cell (B-PLL) and T-cell (T-PLL) prolymphocytic leukemias are rare, poor-prognosis lymphoid neoplasms with similar presentation characterized by symptomatic splenomegaly and lymphocytosis. They can be distinguished from each other and from other T- and B-cell leukemias by careful evaluation of morphology, immunophenotyping, and molecular genetics. The clinical behavior is typically aggressive, although a subset of patients may have an indolent phase of variable length. First-line therapy for T-PLL is with intravenous alemtuzumab and for B-PLL is with combination purine analog-based chemo-immunotherapy. New B-cell receptor inhibitors, such as ibrutinib and idelalisib, may have a role in the management of B-PLL, especially for the patients harboring abnormalities of TP53. Allogenic stem cell transplantation should still be considered for eligible patients and may be the only current therapy capable of delivering a cure. In the past few years, many of the molecular mechanisms underlying disease pathogenesis and progression have been revealed and are likely to lead to the development of novel targeted approaches.

Classic and Novel Signaling Pathways Involved in Cancer: Targeting the NF-κB and Syk Signaling Pathways

2019 ◽  
Vol 14 (3) ◽  
pp. 219-225 ◽  
Author(s):  
Cong Tang ◽  
Guodong Zhu
Keyword(s):  
Cancer Therapy ◽  
Tyrosine Kinase ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Cell Receptor ◽  
Transmembrane Receptors ◽  
Biological Responses ◽  
Different Types

The nuclear factor kappa B (NF-κB) consists of a family of transcription factors involved in the regulation of a wide variety of biological responses. Growing evidence support that NF-κB plays a major role in oncogenesis as well as its well-known function in the regulation of immune responses and inflammation. Therefore, we made a review of the diverse molecular mechanisms by which the NF-κB pathway is constitutively activated in different types of human cancers and the potential role of various oncogenic genes regulated by this transcription factor in cancer development and progression. We also discussed various pharmacological approaches employed to target the deregulated NF-κB signaling pathway and their possible therapeutic potential in cancer therapy. Moreover, Syk (Spleen tyrosine kinase), non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immune-receptors like the B-cell receptor (BCR), which can also activate the inflammasome and NF-κB-mediated transcription of chemokines and cytokines in the presence of pathogens would be discussed as well. The highlight of this review article is to summarize the classic and novel signaling pathways involved in NF-κB and Syk signaling and then raise some possibilities for cancer therapy.

Novel Findings of Anti-cancer Property of Propofol

2018 ◽  
Vol 18 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Jiaqiang Wang ◽  
Chien-shan Cheng ◽  
Yan Lu ◽  
Xiaowei Ding ◽  
Minmin Zhu ◽  
...  
Keyword(s):  
General Anesthesia ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Intravenous Anesthetic ◽  
The Past ◽  
Anti Cancer ◽  
Underlying Mechanisms ◽  
Recent Attention

Background: Propofol, a widely used intravenous anesthetic agent, is traditionally applied for sedation and general anesthesia. Explanation: Recent attention has been drawn to explore the effect and mechanisms of propofol against cancer progression in vitro and in vivo. Specifically, the proliferation-inhibiting and apoptosis-inducing properties of propofol in cancer have been studied. However, the underlying mechanisms remain unclear. Conclusion: This review focused on the findings within the past ten years and aimed to provide a general overview of propofol's malignance-modulating properties and the potential molecular mechanisms.

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