Aktualny pogląd na komórkową funkcję S100A6 i jego ligandów, CacyBP/SIP i Sgt1

Filipek, Anna

doi:10.18388/pb.2018_136

Cited by 10 publications

(15 citation statements)

References 98 publications

(137 reference statements)

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“…S100A6 is a low-molecular-weight Ca 2+ -binding protein of the S100 family [1,2]. It functions as a homodimer mainly formed by non-covalent interactions ( Figure 1) and binds two Ca 2+ per monomer, each through an EF-hand structure consisting of two α helices linked by a short loop region.…”

Section: Introductionmentioning

confidence: 99%

“…S100A6 is present in different mammalian cells and tissues, among them in the brain [5,6] where it is present in neurons and astrocytes [6,7]. Within the cell, S100A6 is localized mainly in the cytoplasm but, upon increase in intracellular Ca 2+ concentration, may also associate with the nuclear envelope and plasma membrane [1]. Interestingly, S100A6 can be secreted and was found in extracellular matrix and various body fluids [8].…”

Section: Introductionmentioning

confidence: 99%

“…Quite recently, FOR20 (FOP-related protein of 20 kDa), a protein possibly involved in cilia formation, has been identified as a S100A6 ligand [13]. Binding to these ligands suggests that S100A6 plays a regulatory role in cytoskeleton organization and in membrane dynamics [1].…”

Section: Introductionmentioning

confidence: 99%

“…Another group of S100A6 ligands includes transcription factors of the p53 family, namely p53, p63, and p73, and a ubiquitin ligase, MDM2 (mouse double minute 2) [1]. This group of ligands implicates S100A6 in regulation of the stability/activity of p53 family transcription factors and, in consequence, in transcription.…”

Section: Introductionmentioning

confidence: 99%

“…Research conducted by many laboratories concerning S100A6 function revealed a structurally similar but functionally diverse group of S100A6 ligands containing TPR and/or CS domains. This group includes melusin, kinesin light chain, Sgt1 (suppressor of G2 allele of Skp1), Hop (Hsp90/Hsp70-organizing protein), Tom70 (translocase of outer mitochondrial membrane 70), FKBP52 (peptidyl prolyl cis/trans isomerase FK506-binding protein 4), FKBP38 (peptidyl prolyl cis/trans isomerase FK506-binding protein 38), CyP40 (cyclophilin 40), CHIP (C-terminus of Hsc70-interacting protein), PP5 (protein phosphatase 5), and CacyBP/SIP (calcyclin binding protein/Siah-1 interacting protein) [1]. Interaction with these ligands may suggest involvement of S100A6 in cellular stress response, which seems to play a fundamental role in signaling pathways linked to various pathologies including neurodegeneration.…”

Section: Introductionmentioning

confidence: 99%

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S100A6 and Its Brain Ligands in Neurodegenerative Disorders

Filipek

2020

IJMS

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The S100A6 protein is present in different mammalian cells and tissues including the brain. It binds Ca2+ and Zn2+ and interacts with many target proteins/ligands. The best characterized ligands of S100A6, expressed at high level in the brain, include CacyBP/SIP and Sgt1. Research concerning the functional role of S100A6 and these two ligands indicates that they are involved in various signaling pathways that regulate cell proliferation, differentiation, cytoskeletal organization, and others. In this review, we focused on the expression/localization of these proteins in the brain and on their possible role in neurodegenerative diseases. Published results demonstrate that S100A6, CacyBP/SIP, and Sgt1 are expressed in various brain structures and in the spinal cord and can be found in different cell types including neurons and astrocytes. When it comes to their possible involvement in nervous system pathology, it is evident that their expression/level and/or subcellular localization is changed when compared to normal conditions. Among diseases in which such changes have been observed are Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), epileptogenesis, Parkinson’s disease (PD), Huntington’s disease (HD), and others.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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S100A6 and Its Brain Ligands in Neurodegenerative Disorders

Filipek

2020

IJMS

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S100A6 participates in initiation of autoimmune encephalitis and is under epigenetic control

Lin

et al. 2023

Brain and Behavior

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Introduction: Autoimmune encephalitis (AE) is caused by autoantibodies attacking neuronal cell surface antigens and/or synaptic antigens. We previously demonstrated that S100A6 was hypomethylated in patients with AE and that it promoted B lymphocyte infiltration through the simulated blood-brain barrier (BBB). In this study, we focused on the epigenetic regulation of S100A6, the process by which S100A6 affects B lymphocyte infiltration, and the therapeutic potential of S100A6 antibodies. Methods:We enrolled and collected serum from 10 patients with AE and 10 healthy control (HC) subjects. Promoter methylation and 5-azacytidine treatment assays were conducted to observe the methylation process of S100A6. The effect of S100A6 on B lymphocytes was analyzed using an adhesion assay and leukocyte transendothelial migration (LTEM) assay. A LTEM assay was also used to compare the effects of the serum of HCs, serum of AE patients, S100A6 recombinant protein, and S100A6 antibodies on B lymphocytes. Result:The promoter methylation and 5-azacytidine treatment assays confirmed that S100A6 was regulated by DNA methylation. The adhesion study demonstrated that the addition of S100A6 enhanced adhesion between B lymphocytes and a BBB endothelial cell line in a concentration-dependent manner. The LTEM assay showed that the serum of AE patients, as well as S100A6, promoted B lymphocyte infiltration and that this effect could be attenuated by S100A6 antibodies. Conclusion:We clarified that S100A6 was under epigenetic regulation in patients with AE and that it helped B lymphocytes to adhere to and infiltrate the BBB endothelial layer, which could be counteracted by S100A6 antibodies. Therefore, the methylation [Correction added on 15th February 2023, after first online publication: equal contributions of Chih-Hsiang Lin and Sung-Chou Li has been added]This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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S100A6 is a critical regulator of hematopoietic stem cells

et al. 2020

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The fate options of hematopoietic stem cells (HSCs) include self-renewal, differentiation, migration, and apoptosis. HSCs self-renewal divisions in stem cells are required for rapid regeneration during tissue damage and stress, but how precisely intracellular calcium signals are regulated to maintain fate options in normal hematopoiesis is unclear. S100A6 knockout (KO) HSCs have reduced total cell numbers in the HSC compartment, decreased myeloid output, and increased apoptotic HSC numbers in steady state. S100A6KO HSCs had impaired self-renewal and regenerative capacity, not responding to 5-Fluorouracil. Our transcriptomic and proteomic profiling suggested that S100A6 is a critical HSC regulator. Intriguingly, S100A6KO HSCs showed decreased levels of phosphorylated Akt (p-Akt) and Hsp90, with an impairment of mitochondrial respiratory capacity and a reduction of mitochondrial calcium levels. We showed that S100A6 regulates intracellular and mitochondria calcium buffering of HSC upon cytokine stimulation and have demonstrated that Akt activator SC79 reverts the levels of intracellular and mitochondrial calcium in HSC. Hematopoietic colony-forming activity and the Hsp90 activity of S100A6KO are restored through activation of the Akt pathway. We show that p-Akt is the prime downstream mechanism of S100A6 in the regulation of HSC self-renewal by specifically governing mitochondrial metabolic function and Hsp90 protein quality.

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Aktualny pogląd na komórkową funkcję S100A6 i jego ligandów, CacyBP/SIP i Sgt1

Cited by 10 publications

References 98 publications

S100A6 and Its Brain Ligands in Neurodegenerative Disorders

S100A6 and Its Brain Ligands in Neurodegenerative Disorders

S100A6 participates in initiation of autoimmune encephalitis and is under epigenetic control

S100A6 is a critical regulator of hematopoietic stem cells

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