scholarly journals Epigenetic regulation by the menin pathway

2017 ◽  
Vol 24 (10) ◽  
pp. T147-T159 ◽  
Author(s):  
Zijie Feng ◽  
Jian Ma ◽  
Xianxin Hua
Keyword(s):  
Transcription Factors ◽  
Cell Signaling ◽  
Signaling Pathways ◽  
Gene Transcription ◽  
Epigenetic Regulation ◽  
Posttranslational Modifications ◽  
Genetic Model ◽  
Mirna Biogenesis ◽  
Endocrine Organs

There is a trend of increasing prevalence of neuroendocrine tumors (NETs), and the inherited multiple endocrine neoplasia type 1 (MEN1) syndrome serves as a genetic model to investigate how NETs develop and the underlying mechanisms. Menin, encoded by the MEN1 gene, at least partly acts as a scaffold protein by interacting with multiple partners to regulate cellular homeostasis of various endocrine organs. Menin has multiple functions including regulation of several important signaling pathways by controlling gene transcription. Here, we focus on reviewing the recent progress in elucidating the key biochemical role of menin in epigenetic regulation of gene transcription and cell signaling, as well as posttranslational regulation of menin itself. In particular, we will review the progress in studying structural and functional interactions of menin with various histone modifiers and transcription factors such as MLL, PRMT5, SUV39H1 and other transcription factors including c-Myb and JunD. Moreover, the role of menin in regulating cell signaling pathways such as TGF-beta, Wnt and Hedgehog, as well as miRNA biogenesis and processing will be described. Further, the regulation of the MEN1 gene transcription, posttranslational modifications and stability of menin protein will be reviewed. These various modes of regulation by menin as well as regulation of menin by various biological factors broaden the view regarding how menin controls various biological processes in neuroendocrine organ homeostasis.

scholarly journals Ca2+ Microdomains, Calcineurin and the Regulation of Gene Transcription

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 875
Author(s):  
Gerald Thiel ◽  
Tobias Schmidt ◽  
Oliver G. Rössler
Keyword(s):  
Transcription Factors ◽  
Protein Kinase ◽  
Protein Kinases ◽  
Gene Transcription ◽  
Intracellular Signaling ◽  
Second Messengers ◽  
Major Function ◽  
Surface Receptors ◽  
Dependent Protein

Ca2+ ions function as second messengers regulating many intracellular events, including neurotransmitter release, exocytosis, muscle contraction, metabolism and gene transcription. Cells of a multicellular organism express a variety of cell-surface receptors and channels that trigger an increase of the intracellular Ca2+ concentration upon stimulation. The elevated Ca2+ concentration is not uniformly distributed within the cytoplasm but is organized in subcellular microdomains with high and low concentrations of Ca2+ at different locations in the cell. Ca2+ ions are stored and released by intracellular organelles that change the concentration and distribution of Ca2+ ions. A major function of the rise in intracellular Ca2+ is the change of the genetic expression pattern of the cell via the activation of Ca2+-responsive transcription factors. It has been proposed that Ca2+-responsive transcription factors are differently affected by a rise in cytoplasmic versus nuclear Ca2+. Moreover, it has been suggested that the mode of entry determines whether an influx of Ca2+ leads to the stimulation of gene transcription. A rise in cytoplasmic Ca2+ induces an intracellular signaling cascade, involving the activation of the Ca2+/calmodulin-dependent protein phosphatase calcineurin and various protein kinases (protein kinase C, extracellular signal-regulated protein kinase, Ca2+/calmodulin-dependent protein kinases). In this review article, we discuss the concept of gene regulation via elevated Ca2+ concentration in the cytoplasm and the nucleus, the role of Ca2+ entry and the role of enzymes as signal transducers. We give particular emphasis to the regulation of gene transcription by calcineurin, linking protein dephosphorylation with Ca2+ signaling and gene expression.

Is protein context responsible for peptide-mediated interactions?

2019 ◽  
Vol 15 (4) ◽  
pp. 280-295 ◽  
Author(s):  
Peng Zhou ◽  
Qingqing Miao ◽  
Fugang Yan ◽  
Zhongyan Li ◽  
Qianhu Jiang ◽  
...  
Keyword(s):  
Cell Signaling ◽  
Signaling Pathways ◽  
The Stability ◽  
Cell Signaling Pathways

Many cell signaling pathways are orchestrated by the weak, transient, and reversible peptide-mediated interactions (PMIs). Here, the role of protein context in contributing to the stability and specificity of PMIs is investigated systematically.

Scaffold Proteins and their Roles in Human Diseases

2020 ◽  
Vol 14 (01) ◽  
pp. 15-29
Author(s):  
Somsubhro Mukherjee ◽  
Boon Chuan Low
Keyword(s):  
Cell Signaling ◽  
Signaling Pathways ◽  
Drug Targets ◽  
Metabolic Diseases ◽  
Scaffold Proteins ◽  
Human Diseases ◽  
Normal Functions ◽  
Cellular Pathways ◽  
Cell Signaling Pathways

Scaffold proteins are critical regulators of important cell signaling pathways. Though scaffolds are not stringently defined in meaning, they are known to interact with numerous components of a signaling pathway, binding and bridging them into distinct and functional complexes. They control signal transduction and assist the localization of pathway components (organized in complexes) to definite regions of the cell such as the endosomes, plasma membrane, the cytoplasm, mitochondria, Golgi, and the nucleus. Years of research in this field have revealed the versatility of this class of protein and the important role it plays in maintaining the normal functions of the human body. Here, we discuss the role of several scaffold proteins which are implicated in important signaling pathways that play important roles in cardiac diseases, metabolic diseases, neurological disorders, and cancer. Their versatility and functions in human diseases make them attractive drug targets, several of which have been investigated in clinical trials. Future studies of scaffold proteins should give us an in-depth knowledge of how cell signaling works in normal and pathological conditions and would offer avenues to disrupt harmful cellular pathways to circumvent diseases.

The role of melatonin in targeting cell signaling pathways in neurodegeneration

2019 ◽  
Vol 1443 (1) ◽  
pp. 75-96 ◽  
Author(s):  
Mayuri Shukla ◽  
Vorapin Chinchalongporn ◽  
Piyarat Govitrapong ◽  
Russel J. Reiter
Keyword(s):  
Cell Signaling ◽  
Signaling Pathways ◽  
Cell Signaling Pathways

scholarly journals Lipid Rafts: Keys to Sperm Maturation, Fertilization, and Early Embryogenesis

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Natsuko Kawano ◽  
Kaoru Yoshida ◽  
Kenji Miyado ◽  
Manabu Yoshida
Keyword(s):  
Cell Membrane ◽  
Cell Signaling ◽  
Membrane Fusion ◽  
Lipid Rafts ◽  
Gene Transcription ◽  
Early Embryogenesis ◽  
Sperm Maturation ◽  
Protein Receptors ◽  
Structure And Functions

Cell membranes are composed of many different lipids and protein receptors, which are important for regulating intracellular functions and cell signaling. To orchestrate these activities, the cell membrane is compartmentalized into microdomains that are stably or transiently formed. These compartments are called “lipid rafts”. In gamete cells that lack gene transcription, distribution of lipids and proteins on these lipid rafts is focused during changes in their structure and functions such as starting flagella movement and membrane fusion. In this paper, we describe the role of lipid rafts in gamete maturation, fertilization, and early embryogenesis.

T2065 Curcumin Suppresses Intestinal Epithelial Response to Clostridium difficile Infection: Role of Cell Signaling Pathways

2009 ◽  
Vol 136 (5) ◽  
pp. A-631
Author(s):  
Nandakumar Srinivasan ◽  
Dharmalingam Subramaniam ◽  
Aarthi Varman ◽  
Rama P. Ramanujam ◽  
Courtney W. Houchen ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Cell Signaling ◽  
Signaling Pathways ◽  
Clostridium Difficile Infection ◽  
Intestinal Epithelial ◽  
Cell Signaling Pathways

scholarly journals Role of calcification in aortic degeneration

2020 ◽  
Vol 7 (1) ◽  
pp. 6-21
Author(s):  
D. A. Kostina ◽  
V. E. Uspensky ◽  
D. S. Semenova ◽  
A. S. Kostina ◽  
N. V. Boyarskaya ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Signaling Pathways ◽  
Vascular Calcification ◽  
Vascular Pathology ◽  
Signal Pathways ◽  
Vascular Cells ◽  
Metabolic Dysfunction ◽  
Main Attention ◽  
Biological Regulation

Vascular calcification is a widely-spread pathology with high mortality. It is active bioregulated process that is observed in pathogenesis of different desires, associated with metabolic dysfunction, congenital tissue desires and aging. Signal pathways and transcription factors that are involved in vascular calcification are also takes place in normal osteogenesis and/or vascular development. In the review the main attention is payed to the role of signaling pathways BMP (bone morphogenic protein), Notch, Wnt and to the role of transcription factors BMP2, RUNX2, Msx2 in vascular calcification. Probably, dysfunction of osteogenic signal pathways and transdifferentiation of vascular cells to osteoblast-like cells is a common prosses not only for vascular calcification or mineralization, but is a way of vascular degradation in general. Proosteogenic changes at cellular and molecular level may play role in pathogenesis of a disease without manifestation of vascular mineralization, such as thoracic aortic aneurysm. Ability of vascular cells to change their phenotype to osteophenotype is very likely biologically important ability. Over weakness of calcific signaling pathways activity can also lead to vascular pathology. The aim of the review is to overlook the mechanisms of vascular calcification focusing at the role of signal pathways and vascular cells at this process with particular attention to aortic calcification. Understanding the mechanisms of biological regulation of pro- and antiosteogenic processes in pathology and normal conditions opens new opportunities to influence this prosess in order to correct vascular pathologies.

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