scholarly journals WC-1 and the Proximal GATA Sequence Mediate a Cis-/Trans-Acting Repressive Regulation of Light-Dependent Gene Transcription in the Dark

2019 ◽  
Vol 20 (12) ◽  
pp. 2854 ◽  
Author(s):  
Andrea Brenna ◽  
Claudio Talora

Light influences a wide range of physiological processes from prokaryotes to mammals. Neurospora crassa represents an important model system used for studying this signal pathway. At molecular levels, the WHITE COLLAR Complex (WCC), a heterodimer formed by WC-1 (the blue light photo-sensor) and WC-2 (the transcriptional activator), is the critical positive regulator of light-dependent gene expression. GATN (N indicates any other nucleotide) repeats are consensus sequences within the promoters of light-dependent genes recognized by the WCC. The distal GATN is also known as C-box since it is involved in the circadian clock. However, we know very little about the role of the proximal GATN, and the molecular mechanism that controls the transcription of light-induced genes during the dark/light transition it is still unclear. Here we showed a first indication that mutagenesis of the proximal GATA sequence within the target promoter of the albino-3 gene or deletion of the WC-1 zinc finger domain led to a rise in expression of light-dependent genes already in the dark, effectively decoupling light stimuli and transcriptional activation. This is the first observation of cis-/trans-acting repressive machinery, which is not consistent with the light-dependent regulatory mechanism observed in the eukaryotic world so far.

2021 ◽  
Vol 22 (12) ◽  
pp. 6403
Author(s):  
Md Saidur Rahman ◽  
Khandkar Shaharina Hossain ◽  
Sharnali Das ◽  
Sushmita Kundu ◽  
Elikanah Olusayo Adegoke ◽  
...  

Insulin is a polypeptide hormone mainly secreted by β cells in the islets of Langerhans of the pancreas. The hormone potentially coordinates with glucagon to modulate blood glucose levels; insulin acts via an anabolic pathway, while glucagon performs catabolic functions. Insulin regulates glucose levels in the bloodstream and induces glucose storage in the liver, muscles, and adipose tissue, resulting in overall weight gain. The modulation of a wide range of physiological processes by insulin makes its synthesis and levels critical in the onset and progression of several chronic diseases. Although clinical and basic research has made significant progress in understanding the role of insulin in several pathophysiological processes, many aspects of these functions have yet to be elucidated. This review provides an update on insulin secretion and regulation, and its physiological roles and functions in different organs and cells, and implications to overall health. We cast light on recent advances in insulin-signaling targeted therapies, the protective effects of insulin signaling activators against disease, and recommendations and directions for future research.


2020 ◽  
pp. e427
Author(s):  
Katarzyna Papierska ◽  
Violetta Krajka-Kuźniak

Colorectal cancer is a malignant tumour of the digestive system, more common in the elderly than in younger individuals. The incidence rate in the United States and the European Union is increasing by an average of 4.2% to 4.6% annually. There is emerging evidence that deregulation of the signalling pathway and abnormal expression and activation of genes is the main reason for the development of colorectal cancer. Signal transducer and activator of transcription (STAT3) is a transcription factor of signal transduction and transcriptional activation of target genes which plays important roles in proliferation, differentiation, apoptosis and other physiological processes. It has been confirmed that abnormal activation of STAT3 is involved in the development of tumours, so the identification of STAT3 inhibitors is a promising strategy for cancer chemoprevention and treatment of colorectal cancer. In this review, the roles of STAT3 in the pathogenesis and treatment of colorectal cancer are discussed.


2021 ◽  
pp. 153537022110618
Author(s):  
Mao Li ◽  
Xingfeng Xu ◽  
Yan Su ◽  
Xiaoyun Shao ◽  
Yali Zhou ◽  
...  

PPM1A (magnesium-dependent phosphatase 1 A, also known as PP2Cα) is a member of the Ser/Thr protein phosphatase family. Protein phosphatases catalyze the removal of phosphate groups from proteins via hydrolysis, thus opposing the role of protein kinases. The PP2C family is generally considered a negative regulator in the eukaryotic stress response pathway. PPM1A can bind and dephosphorylate various proteins and is therefore involved in the regulation of a wide range of physiological processes. It plays a crucial role in transcriptional regulation, cell proliferation, and apoptosis and has been suggested to be closely related to the occurrence and development of cancers of the lung, bladder, and breast, amongst others. Moreover, it is closely related to certain autoimmune diseases and neurodegenerative diseases. In this review, we provide an insight into currently available knowledge of PPM1A, including its structure, biological function, involvement in signaling pathways, and association with diseases. Lastly, we discuss whether PPM1A could be targeted for therapy of certain human conditions.


2021 ◽  
Vol 7 (1) ◽  
pp. 16
Author(s):  
Didem Karakas ◽  
Bulent Ozpolat

Long non-coding RNAs (lncRNAs), a group of non-protein coding RNAs with lengths of more than 200 nucleotides, exert their effects by binding to DNA, mRNA, microRNA, and proteins and regulate gene expression at the transcriptional, post-transcriptional, translational, and post-translational levels. Depending on cellular location, lncRNAs are involved in a wide range of cellular functions, including chromatin modification, transcriptional activation, transcriptional interference, scaffolding and regulation of translational machinery. This review highlights recent studies on lncRNAs in the regulation of protein translation by modulating the translational factors (i.e, eIF4E, eIF4G, eIF4A, 4E-BP1, eEF5A) and signaling pathways involved in this process as wells as their potential roles as tumor suppressors or tumor promoters.


2019 ◽  
Vol 14 (2) ◽  
pp. 70-85
Author(s):  
T. A. Kovalenko ◽  
M. A. Panteleev ◽  
A. N. Sveshnikova

Tissue factor, being the main initiator of the blood coagulation in vivo, is involved in a number of physiological processes, such as angiogenesis or cell migration. These processes are not only significant for normal physiology, but also play a role in the development and progression of oncological diseases. This review presents data on the structure of tissue factor, its expression in normal conditions and in cancer, its role in thrombosis development associated with cancer, in angiogenesis and in metastasis. The involvement of tissue factor in such a wide range of physiological processes important for the progression of cancer makes it an attractive target molecule for therapy.


2021 ◽  
Vol 8 ◽  
Author(s):  
Che-Yuan Hsu ◽  
Teruki Yanagi ◽  
Hideyuki Ujiie

Tripartite motif (TRIM) proteins play important roles in a wide range of cell physiological processes, such as signal transduction, transcriptional regulation, innate immunity, and programmed cell death. TRIM29 protein, encoded by the ATDC gene, belongs to the RING-less group of TRIM protein family members. It consists of four zinc finger motifs in a B-box domain and a coiled-coil domain, and makes use of the B-box domain as E3 ubiquitin ligase in place of the RING. TRIM29 was found to be involved in the formation of homodimers and heterodimers in relation to DNA binding; additional studies have also demonstrated its role in carcinogenesis, DNA damage signaling, and the suppression of radiosensitivity. Recently, we reported that TRIM29 interacts with keratins and FAM83H to regulate keratin distribution. Further, in cutaneous SCC, the expression of TRIM29 is silenced by DNA methylation, leading to the loss of TRIM29 and promotion of keratinocyte migration. This paper reviews the role of TRIM family proteins in malignant tumors, especially the role of TRIM29 in cutaneous SCC.


2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Wayne Briner

The proteins that regulate the metabolism of a metal must also play a role in regulating the redox activity of the metal. Metals are intrinsic to a substantial number of biological processes and the proteins that regulate those activities are also considerable in number. The role these proteins play in a wide range of physiological processes involves them directly and indirectly in a variety of disease processes. Similarly, it may be therapeutically advantageous to pharmacologically alter the activity of these metal containing proteins to influence disease processes. This paper will introduce the reader to a number of important proteins in both metal metabolism and oxidative stress, with an emphasis on the brain. Potential pharmacological targets will be considered.


2014 ◽  
pp. 409-420 ◽  
Author(s):  
Z. PAPÁČKOVÁ ◽  
M. CAHOVÁ

Autophagy is the basic catabolic mechanism that involves degradation of dysfunctional cellular components through the action of lysosome as well as supplying energy and compounds for the synthesis of essential biomacromolecules. This process enables cells to survive stress from the external environment like nutrient deprivation. Autophagy is important in the breakdown of proteins, carbohydrates and lipids as well. Furthermore, recent studies have shown that autophagy is critical in wide range of normal human physiological processes, and defective autophagy is associated with diverse diseases, including lysosomal storage disease, myopathies, neurodegeneration and various metabolic disorders. This review summarizes the most up-to-date findings on what role autophagy plays in metabolism.


2016 ◽  
Vol 473 (13) ◽  
pp. 1831-1844 ◽  
Author(s):  
Mohamad Rima ◽  
Marwa Daghsni ◽  
Ziad Fajloun ◽  
Ridha M'rad ◽  
Juan L. Brusés ◽  
...  

Calcium plays a key role in cell signalling by its intervention in a wide range of physiological processes. Its entry into cells occurs mainly via voltage-gated calcium channels (VGCC), which are found not only in the plasma membrane of excitable cells but also in cells insensitive to electrical signals. VGCC are composed of different subunits, α1, β, α2δ and γ, among which the cytosolic β subunit (Cavβ) controls the trafficking of the channel to the plasma membrane, its regulation and its gating properties. For many years, these were the main functions associated with Cavβ. However, a growing number of proteins have been found to interact with Cavβ, emphasizing the multifunctional role of this versatile protein. Interestingly, some of the newly assigned functions of Cavβ are independent of its role in the regulation of VGCC, and thus further increase its functional roles. Based on the identity of Cavβ protein partners, this review emphasizes the diverse cellular functions of Cavβ and summarizes both past findings as well as recent progress in the understanding of VGCC.


Author(s):  
Jyoti Das ◽  
Mahak Tiwari ◽  
Deepa Subramanyam

Clathrin is a cytosolic protein involved in the intracellular trafficking of a wide range of cargo. It is composed of three heavy chains and three light chains that together form a triskelion, the subunit that polymerizes to form a clathrin coated vesicle. In addition to its role in membrane trafficking, clathrin is also involved in various cellular and biological processes such as chromosomal segregation during mitosis and organelle biogenesis. Although the role of the heavy chains in regulating important physiological processes has been well documented, we still lack a complete understanding of how clathrin light chains regulate membrane traffic and cell signaling. This review highlights the importance and contributions of clathrin light chains in regulating clathrin assembly, vesicle formation, endocytosis of selective receptors and physiological and developmental processes.


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