Glycogen synthesis and beyond, a comprehensive review of GSK3 as a key regulator of metabolic pathways and a therapeutic target for treating metabolic diseases

Medicinal Research Reviews, Journal Year: 2021, Volume and Issue: 42(2), P. 946 - 982

Published: Nov. 3, 2021

Abstract Glycogen synthase kinase‐3 (GSK3) is a highly evolutionarily conserved serine/threonine protein kinase first identified as an enzyme that regulates glycogen (GS) in response to insulin stimulation, which involves GSK3 regulation of glucose metabolism and energy homeostasis. Both isoforms GSK3, GSK3α, GSK3β, have been implicated many biological pathophysiological processes. The various functions are indicated by its widespread distribution multiple cell types tissues. studies activity using animal models the observed effects GSK3‐specific inhibitors provide more insights into roles regulating cross‐talk between some important regulators sensors mitochondrial component function further highlight molecular mechanisms involved regulate metabolic activity, beyond classical regulatory effect on GS. In this review, we summarize specific tissues tightly associated with development disorders. We also address impacts function, regulation. application clinical tests will be highlighted too. Interactions GSK3‐mediated responses different stresses related described brief overview previously less‐appreciated diseases through GS other functions.

Language: Английский

---

QKI shuttles internal m7G-modified transcripts into stress granules and modulates mRNA metabolism

Cell, Journal Year: 2023, Volume and Issue: 186(15), P. 3208 - 3226.e27

Published: June 27, 2023

Language: Английский

---

Wnt/β-Catenin Signaling Pathway in the Development and Progression of Colorectal Cancer

Cancer Management and Research, Journal Year: 2023, Volume and Issue: Volume 15, P. 435 - 448

Published: May 1, 2023

Abstract: The Wnt/β-catenin signaling pathway is a growth control involved in various biological processes as well the development and progression of cancer. Colorectal cancer (CRC) one most common malignancies world. hyperactivation Wnt observed almost all CRC plays crucial role cancer-related such stem cell (CSC) propagation, angiogenesis, epithelial-mesenchymal transition (EMT), chemoresistance, metastasis. This review will discuss how carcinogenesis related therapeutic approaches. Keywords: pathway, colorectal carcinogenesis, APC, therapy

Language: Английский

---

Regulation of Wnt Signaling through Ubiquitination and Deubiquitination in Cancers

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(11), P. 3904 - 3904

Published: May 30, 2020

The Wnt signaling pathway plays important roles in embryonic development, homeostatic processes, cell differentiation, polarity, proliferation, and migration via the β-catenin binding of target genes. Dysregulation is associated with various diseases such as cancer, aging, Alzheimer's disease, metabolic pigmentation disorders. Numerous studies entailing have been conducted for cancers. Diverse factors mediate up- or down-regulation through post-translational modifications (PTMs), aberrant regulation several different malignancies humans. Of numerous PTMs involved, most are regulated by ubiquitination deubiquitination. Ubiquitination E3 ligase attaches ubiquitins to proteins usually induces proteasomal degradation β-catenin, Axin, GSK3, Dvl. Conversely, deubiquitination induced deubiquitinating enzymes (DUBs) detaches modulates stability factors. In this review, we discuss effects on pathway, inhibitors DUBs that can be applied cancer therapeutic strategies.

Language: Английский

---

The Role of Pontin and Reptin in Cellular Physiology and Cancer Etiology

Frontiers in Molecular Biosciences, Journal Year: 2017, Volume and Issue: 4

Published: Aug. 24, 2017

Pontin (RUVBL1, TIP49, TIP49a, Rvb1) and Reptin (RUVBL2, TIP48, TIP49b, Rvb2) are highly conserved ATPases of the AAA+ (ATPases Associated with various cellular Activities) superfamily involved in processes that important for oncogenesis. First identified as being upregulated hepatocellular carcinoma colorectal cancer, their overexpression has since been shown multiple cancer types such breast, lung, gastric, esophageal, pancreatic, kidney, bladder well lymphatic, leukemic cancers. However, exact functions still quite unknown they interact many molecular complexes vastly different downstream effectors. Within nucleus, participate TIP60 INO80 chromatin remodeling. Although not transcription factors themselves, modulate transcriptional activities bona fide proto-oncogenes MYC β-catenin. They associate proteins DNA damage repair PIKK core complex Fanconi anemia pathway. have also to be cell cycle progression, assembly telomerase, mitotic spindle, RNA polymerase II, snoRNPs. When two localize cytoplasm, were reported promote invasion metastasis. Due roles carcinogenesis, it is surprising proving biomarkers diagnosis prognosis current targets development new therapeutic anticancer drugs.

Language: Английский

---

GSK3: A Kinase Balancing Promotion and Resolution of Inflammation

Cells, Journal Year: 2020, Volume and Issue: 9(4), P. 820 - 820

Published: March 28, 2020

GSK3 has been implicated for years in the regulation of inflammation and addressed a plethora scientific reports using variety experimental (disease) models approaches. However, specific role inflammatory process is still not fully understood controversially discussed. Following detailed overview structure, function, various regulatory levels, this review focusses on immunoregulatory functions GSK3, including current knowledge obtained from animal models. Its impact pro-inflammatory cytokine/chemokine profiles, bacterial/viral infections, modulation associated transcriptional signaling pathways Moreover, contributes to resolution multiple e.g., via pro-resolving mediators, clearance apoptotic immune cells, tissue repair processes. The influence development different forms stimulation tolerance also addressed. Collectively, as kinase balancing initiation/perpetuation amelioration/resolution highlighted.

Language: Английский

---

The PI3K/Akt/GSK-3β/ROS/eIF2B pathway promotes breast cancer growth and metastasis via suppression of NK cell cytotoxicity and tumor cell susceptibility

Cancer Biology and Medicine, Journal Year: 2019, Volume and Issue: 16(1), P. 38 - 38

Published: Jan. 1, 2019

Objective: To examine the effect of pSer9-GSK-3β on breast cancer and to determine whether underlying metabolic immunological mechanism is associated with ROS/eIF2B natural killer (NK) cells. Methods: We employed TWS119 inactivate GSK-3β by phosphorylating Ser9 explored its NK The expression GSK-3β, group 2 member D (NKG2D) ligands, eIF2B was quantified PCR Western blot. measured intracellular reactive oxygen species (ROS) mitochondrial ROS using DCFH-DA MitoSOX^TM probe, respectively, conducted quantitative analysis cellular respiration 4T1 cells respiratory chain complex I/III kits. Results: Our investigation revealed that downregulated NKG2D ligands (H60a Rae1), suppressed cytotoxicity cells, promoted migration murine Nevertheless, LY290042, which attenuates p-GSK-3β formation inhibiting PI3K/Akt pathway, reversed these effects. also found higher induced levels ROS, observed abnormality function dysfunction GSK-3β-induced electron transport chain, naturally disturbing level. In addition, NOX3 NOX4 significantly up-regulated, affected generation metastasis cancer. Furthermore, we pSer535-eIF2B (Mult-1 Rae1) following ROS. Conclusions: PI3K/Akt/GSK-3β/ROS/eIF2B pathway could regulate cell activity sensitivity tumor resulted in growth lung metastasis. Thus, a promising target anti-tumor therapy.

Language: Английский

---

Glycogen synthase kinases: Moonlighting proteins with theranostic potential in cancer

Seminars in Cancer Biology, Journal Year: 2018, Volume and Issue: 56, P. 25 - 36

Published: Jan. 5, 2018

Language: Английский

---

North African Medicinal Plants Traditionally Used in Cancer Therapy

Frontiers in Pharmacology, Journal Year: 2017, Volume and Issue: 8

Published: June 26, 2017

Background: Cancer is a major cause of mortality worldwide with increasing numbers by the years. In North Africa, number cancer patients alarming. Also shocking that huge only have access to traditional medicines due several factors, e.g. economic difficulties. fact, medicinal plants are widely used for treatment pathologies, including cancer. Truthfully, herbalists and botanists in African countries prescribe treatment. Despite popularity potential cancer, scientific evidence on their anticancer effects still scarce most described plants. Objective: Bearing mind lack comprehensive systematic studies, aim this review give an overview namely ethnobotanical surveys experimental regarding Africa therapy Method: The research was conducted popular search engines PubMed, Science Direct, Scopus Web Science. focused primarily English written papers published between years 2000 2016. Results: This traditionally highlights Morocco Algeria use folk medicine. Among plethora used, Nigella sativa Trigonella foenum-graecum referred ones Moreover, qualifies them as candidates further drug development. Furthermore, we report underlying cellular molecular mechanisms. Conclusion: Overall, therapeutic some agents. flora offers rich source wide array diseases, elucidation modes action represents indispensable condition rational development new drugs testing activity vivo clinical trials warranted explore full therapy.

Language: Английский

---

Glycogen Synthase Kinase 3β in Cancer Biology and Treatment

Cells, Journal Year: 2020, Volume and Issue: 9(6), P. 1388 - 1388

Published: June 3, 2020

Glycogen synthase kinase (GSK)3β is a multifunctional serine/threonine protein with more than 100 substrates and interacting molecules. GSK3β normally active in cells negative regulation of activity via phosphorylation its serine 9 residue required for most normal to maintain homeostasis. Aberrant expression contributes the pathogenesis progression common recalcitrant diseases such as glucose intolerance, neurodegenerative disorders cancer. Despite recognized roles against several proto-oncoproteins mediators epithelial–mesenchymal transition, deregulated also participates tumor cell survival, evasion apoptosis, proliferation invasion, well sustaining cancer stemness inducing therapy resistance. A therapeutic effect from inhibition has been demonstrated 25 different types. Moreover, there increasing evidence that protects tissues harmful effects associated conventional therapies. Here, we review supporting aberrant hallmark property highlight beneficial on during therapy. The biological rationale targeting treatment discussed at length.

Language: Английский

---