scholarly journals The JNK Signaling Pathway in Inflammatory Skin Disorders and Cancer

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 857 ◽  
Author(s):  
Manel Hammouda ◽  
Amy Ford ◽  
Yuan Liu ◽  
Jennifer Zhang
Keyword(s):  
Cell Carcinoma ◽  
Skin Disorders ◽  
Jnk Pathway ◽  
Jnk Signaling ◽  
Cellular Processes ◽  
Downstream Effector ◽  
Wide Range ◽  
Mitogen Activated Protein ◽  
Common Skin ◽  
Apoptosis And Inflammation

The c-Jun N-terminal kinases (JNKs), with its members JNK1, JNK2, and JNK3, is a subfamily of (MAPK) mitogen-activated protein kinases. JNK signaling regulates a wide range of cellular processes, including cell proliferation, differentiation, survival, apoptosis, and inflammation. Dysregulation of JNK pathway is associated with a wide range of immune disorders and cancer. Our objective is to provide a review of JNK proteins and their upstream regulators and downstream effector molecules in common skin disorders, including psoriasis, dermal fibrosis, scleroderma, basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma.

scholarly journals JNK Signaling: Regulation and Functions Based on Complex Protein-Protein Partnerships

2016 ◽  
Vol 80 (3) ◽  
pp. 793-835 ◽  
Author(s):  
András Zeke ◽  
Mariya Misheva ◽  
Attila Reményi ◽  
Marie A. Bogoyevitch
Keyword(s):  
Current Knowledge ◽  
Eukaryotic Cell ◽  
Membrane Receptors ◽  
Mitogen Activated Protein Kinase ◽  
Jnk Pathway ◽  
Jnk Signaling ◽  
Cytoplasmic Proteins ◽  
Wide Range ◽  
Complex Protein ◽  
Mitogen Activated Protein

SUMMARYThe c-Jun N-terminal kinases (JNKs), as members of the mitogen-activated protein kinase (MAPK) family, mediate eukaryotic cell responses to a wide range of abiotic and biotic stress insults. JNKs also regulate important physiological processes, including neuronal functions, immunological actions, and embryonic development, via their impact on gene expression, cytoskeletal protein dynamics, and cell death/survival pathways. Although the JNK pathway has been under study for >20 years, its complexity is still perplexing, with multiple protein partners of JNKs underlying the diversity of actions. Here we review the current knowledge of JNK structure and isoforms as well as the partnerships of JNKs with a range of intracellular proteins. Many of these proteins are direct substrates of the JNKs. We analyzed almost 100 of these target proteins in detail within a framework of their classification based on their regulation by JNKs. Examples of these JNK substrates include a diverse assortment of nuclear transcription factors (Jun, ATF2, Myc, Elk1), cytoplasmic proteins involved in cytoskeleton regulation (DCX, Tau, WDR62) or vesicular transport (JIP1, JIP3), cell membrane receptors (BMPR2), and mitochondrial proteins (Mcl1, Bim). In addition, because upstream signaling components impact JNK activity, we critically assessed the involvement of signaling scaffolds and the roles of feedback mechanisms in the JNK pathway. Despite a clarification of many regulatory events in JNK-dependent signaling during the past decade, many other structural and mechanistic insights are just beginning to be revealed. These advances open new opportunities to understand the role of JNK signaling in diverse physiological and pathophysiological states.

scholarly journals The PI3K/Akt Pathway: Emerging Roles in Skin Homeostasis and a Group of Non-Malignant Skin Disorders

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1219
Author(s):  
Yan Teng ◽  
Yibin Fan ◽  
Jingwen Ma ◽  
Wei Lu ◽  
Na Liu ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Akt Pathway ◽  
Skin Disorders ◽  
Phosphatidylinositol 3 Kinase ◽  
Skin Development ◽  
Wide Range ◽  
Malignant Skin ◽  
Solid Foundation ◽  
And Migration ◽  
Poor Outcomes

The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway regulates cell proliferation, differentiation, and migration, along with angiogenesis and metabolism. Additionally, it could mediate skin development and homeostasis. There is much evidence to suggest that dysregulation of PI3K/Akt pathway is frequently associated with several human cutaneous malignancies like malignant melanoma (MM), basal cell carcinoma (BCC), and cutaneous squamous cell carcinoma (SCC), as well as their poor outcomes. Nevertheless, emerging roles of PI3K/Akt pathway cascade in a group of common non-malignant skin disorders including acne and psoriasis, among others, have been recognized. The enhanced understanding of dysfunction of PI3K/Akt pathway in patients with these non-malignant disorders has offered a solid foundation for the progress of updated therapeutic targets. This article reviews the latest advances in the roles of PI3K/Akt pathway and their targets in the skin homeostasis and progression of a wide range of non-malignant skin disorders and describes the current progress in preclinical and clinical researches on the involvement of PI3K/Akt pathway targeted therapies.

scholarly journals The Roles of c-Jun N-Terminal Kinase (JNK) in Infectious Diseases

2021 ◽  
Vol 22 (17) ◽  
pp. 9640
Author(s):  
Jing Chen ◽  
Chao Ye ◽  
Chao Wan ◽  
Gang Li ◽  
Lianci Peng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Infectious Diseases ◽  
Protein Kinases ◽  
Therapeutic Agents ◽  
Inflammasome Activation ◽  
Mitogen Activated Protein Kinases ◽  
Jnk Signaling ◽  
Cellular Processes ◽  
Prevention And Treatment ◽  
Mitogen Activated Protein

c-Jun N-terminal kinases (JNKs) are among the most crucial mitogen-activated protein kinases (MAPKs) and regulate various cellular processes, including cell proliferation, apoptosis, autophagy, and inflammation. Microbes heavily rely on cellular signaling pathways for their effective replication; hence, JNKs may play important roles in infectious diseases. In this review, we describe the basic signaling properties of MAPKs and JNKs in apoptosis, autophagy, and inflammasome activation. Furthermore, we discuss the roles of JNKs in various infectious diseases induced by viruses, bacteria, fungi, and parasites, as well as their potential to serve as targets for the development of therapeutic agents for infectious diseases. We expect this review to expand our understanding of the JNK signaling pathway’s role in infectious diseases and provide important clues for the prevention and treatment of infectious diseases.

Integumentary system

2010 ◽  
Author(s):  
Jacinta Kelly ◽  
Joan Simons
Keyword(s):  
Skin Diseases ◽  
Normal Structure ◽  
The Body ◽  
Mechanical Trauma ◽  
Skin Disorders ◽  
Nursing Management ◽  
Anatomy And Physiology ◽  
System P ◽  
Wide Range ◽  
Common Skin

The skin is an organ that serves many functions in maintaining homeostasis in the body (Bryant, 2000). A wide range of diseases manifest in changes in the skin and its appendages, and because the skin is visible and its disorders are often disfiguring, skin disorders can cause emotional and psychological stress for children and their families (Ball & Bindler, 2007). Skin diseases affect 20–33% of the population at any one time, seriously interfering with activities in 10% (Byrant, 2000). Epidemiological evidence suggests that many cases of skin disease do not reach the general practitioner (GP) or even the local pharmacist; nevertheless, each year about 15% of the population consult their GPs about skin complaints (Bryant, 2000). Skin disorders are among the most common health problems in children (Butcher & White, 2005). The infant and child are possibly more vulnerable to the effects of skin disorders and breakdown due to their underdeveloped integumentary system. Understanding the normal condition of the skin can help in the identification of abnormal signs and prompt treatment of skin disorders (Butcher & White, 2005). This chapter will focus on the integumentary system of the child, with reference to the normal structure of the skin together with common alterations and injuries to the skin of the child and the skills required for their nursing management. At the end of this chapter you should be able to do the following: ● Understand the normal child skin anatomy and physiology. ● Understand the fundamentals of a skin assessment in a child. ● Develop an awareness of the management of common skin alterations. ● Understand the nature and treatment of a child with a skin injury. The skin of an infant or child is normally fundamentally the same as that of an adult, although the blood and nerve supplies are immature and the dermis thinner, with less collagen and fewer elastic fibres. This means that the skin is fragile and can be more easily damaged through physical and mechanical trauma (Turnball, 2007). The skin of a newborn is found to have lanugo, which is a very fine, soft, and unpigmented coat of hairs covering its body until it is shed about 14 days after birth.

JNK Signaling Pathway Mediates Fluoride-Induced Upregulation of CK1α during Enamel Formation

2021 ◽  
pp. 1-9
Author(s):  
Zhongrui Yang ◽  
Guanghui Shi ◽  
Jing Guo ◽  
Yanyan Zhou ◽  
Jie Jia
Keyword(s):  
Signaling Pathways ◽  
Dental Fluorosis ◽  
Control Group ◽  
Molecular Signaling ◽  
Fluoride Level ◽  
Jnk Pathway ◽  
Jnk Signaling ◽  
Cellular Processes ◽  
High Fluoride ◽  
Jnk Signaling Pathway

Fluorosis is a defect in the enamel mineral content caused by excessive fluoride intake during amelogenesis; the interaction of various factors in the development and progression of fluorosis has not been defined. Casein kinase 1α (CK1α) is constitutively active in cells and is involved in diverse cellular processes; however, its expression in fluorosis has not been measured. This study aimed to investigate the effects of fluoride on CK1α expression and to assess the regulation of molecular signaling involving fluoride and CK1α during enamel development. Kunming mice were randomly divided into the control and F groups with induced clinical features of fluorosis. The F group mice, including mothers and newborns, were treated with 50 ppm fluoridated water. Immunohistochemical staining of the sections of the embryonic mandible regions was performed at the bell stage. Protein expression and signaling pathways in a mouse-derived ameloblast-like cell line (LS8) exposed to fluoride or a Jun N-terminal kinase (JNK) inhibitor were compared to those in control cells without exposure. CK1α and proteins of the JNK signaling pathways were assayed by quantitative real-time PCR and Western blotting. Mice of the F group developed dental fluorosis. Scanning electron microscopy showed a significant reduction in the degree of mineralization in the F group mice, which manifested as thin, loosely arranged, and disorganized enamel rods. Additional analysis revealed that the expression of CK1α in the F group was significantly elevated compared with that in the control group; LS8 cells responded to fluoride by upregulation of CK1α expression through the JNK pathway. Our findings identified the potential effects of CK1α on fluorosis using a mouse model and revealed that a high fluoride level increases the expression of CK1α and that JNK can be a key regulatory factor in CK1α expression.

Association of Ras-Raf-MEK-Erk/JNK pathway mutations with overall survival for lung squamous cell carcinoma patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14754-e14754
Author(s):  
Long Xu ◽  
Ming Liu ◽  
Tanxiao Huang ◽  
Suo Peisu ◽  
Lele Song ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Lung Squamous Cell Carcinoma ◽  
Rank Test ◽  
Jnk Pathway ◽  
Jnk Signaling ◽  
Log Rank Test ◽  
Jnk Signaling Pathway

e14754 Background: Genomic alterations often lead to aberrant signaling pathways which play an important role in tumorigenesis and development. Here we report the mutational status of genes associated with the Ras-Raf-MEK-Erk/JNK signaling pathway as a biomarker for predicting overall survival (OS) for Lung squamous cell carcinoma (SQCC) patients. Methods: We used the cBioPortal platform to analyze a cohort of 494 SQCC samples from TCGA data. The general Ras-Raf-MEK-Erk/JNK signaling pathway includes 26 genes (KRAS, HRAS, BRAF, RAF1, MAP3K1, MAP3K2, MAP3K3, MAP3K4, MAP3K5, MAP2K1, MAP2K2, MAP2K3, MAP2K4, MAP2K5, MAPK1, MAPK3, MAPK4, MAPK6, MAPK7, MAPK8, MAPK9, MAPK12, MAPK14, DAB2, RASSF1, RAB25). We analyzed the number of samples with/without mutations in the Ras-Raf-MEK-Erk/JNK pathway and found is 214 and 284 that had, or didn’t have, mutations in this pathway, respectively. The overall survival of these two groups was analyzed using the Kaplan-Meier Estimate, and the statistical difference between these groups was calculated using the log-rank test afterwards. Results: The log-rank test p-value is 2.086e-3, which indicates a significant difference in the overall survival between the two groups. It shows that the group with alterations in the Ras-Raf-MEK-Erk/JNK signaling pathway had a longer overall survival than the group without those alterations. The details are as follows: Conclusions: Ras-Raf-MEK-Erk/JNK pathway mutations are significantly associated with longer OS for lung SQCC patients. Mutations in this pathway can be a potential indicator for SQCC patients, but the biological reasons behind this relationship remain to be explored.[Table: see text]

scholarly journals Oncogenic ALKF1174L drives tumorigenesis in cutaneous squamous cell carcinoma

2020 ◽  
Vol 3 (6) ◽  
pp. e201900601
Author(s):  
Marco Gualandi ◽  
Maria Iorio ◽  
Olivia Engeler ◽  
André Serra-Roma ◽  
Giuseppe Gasparre ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Cell Of Origin ◽  
Anaplastic Lymphoma ◽  
Downstream Effector ◽  
Tumorigenic Potential ◽  
Common Skin ◽  
First Time

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer characterized by increased mortality. Here, we show for the first time that anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase of the insulin receptor superfamily, plays a pivotal role in the pathogenesis of cSCC. Our data demonstrate that the overexpression of the constitutively active, mutated ALK, ALKF1174L, is sufficient to initiate the development of cSCC and is 100% penetrant. Moreover, we show that cSCC development upon ALKF1174L overexpression is independent of the cell-of-origin. Molecularly, our data demonstrate that ALKF1174L cooperates with oncogenic KrasG12D and loss of p53, well-established events in the biology of cSCC. This cooperation results in a more aggressive cSCC type associated with a higher grade histological morphology. Finally, we demonstrate that Stat3 is a key downstream effector of ALKF1174L and likely plays a role in ALKF1174L-driven cSCC tumorigenesis. In sum, these findings reveal that ALK can exert its tumorigenic potential via cooperation with multiple pathways crucial in the pathogenesis of cSCC. Finally, we show that human cSCCs contain mutations in the ALK gene. Taken together, our data identify ALK as a new key player in the pathogenesis of cSCC, and this knowledge suggests that oncogenic ALK signaling can be a target for future clinical trials.

scholarly journals The Jun N-terminal kinases signaling pathway plays a “seesaw” role in ovarian carcinoma: a molecular aspect

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Yingyu Dou ◽  
Xiaoyan Jiang ◽  
Hui Xie ◽  
Junyu He ◽  
Songshu Xiao
Keyword(s):  
Ovarian Cancer ◽  
Signaling Pathway ◽  
Driving Forces ◽  
Mapk Signaling ◽  
Jnk Pathway ◽  
Jnk Signaling ◽  
Gynecological Malignancy ◽  
Mitogen Activated Protein ◽  
Jnk Inhibitors ◽  
Jnk Signaling Pathway

Abstract Ovarian cancer is the most common gynecological malignancy that causes cancer-related deaths in women today; this being the case, developing an understanding of ovarian cancer has become one of the major driving forces behind cancer research overall. Moreover, such research over the last 20 years has shown that the Jun N-terminal kinase (JNK) signaling pathway plays an important role in regulating cell death, survival, growth and proliferation in the mitogen-activated protein kinases (MAPK) signaling pathway, an important pathway in the formation of cancer. Furthermore, the JNK signaling pathway is often regulated by an abnormal activation in human tumors and is frequently reported in the literature for its effect on the progression of ovarian cancer. Although the FDA has approved some JNK inhibitors for melanoma, the agency has not approved JNK inhibitors for ovarian cancer. However, there are some experimental data on inhibitors and activators of the JNK signaling pathway in ovarian cancer, but related clinical trials need to be further improved. Although the Jun N-terminal kinase (JNK) signaling pathway is implicated in the formation of cancer in general, research has also indicated that it has a role in suppressing cancer as well. Here, we summarize this seemingly contradictory role of the JNK signaling pathway in ovarian cancer, that ‘seesaws’ between promoting and suppressing cancer, as well as summarizing the application of several JNK pathway inhibitors in cancer in general, and ovarian cancer in particular.

scholarly journals Role of p90RSK in Kidney and Other Diseases

2019 ◽  
Vol 20 (4) ◽  
pp. 972 ◽  
Author(s):  
Ling Lin ◽  
Samantha White ◽  
Kebin Hu
Keyword(s):  
Kidney Diseases ◽  
Critical Role ◽  
Mitogen Activated Protein Kinase ◽  
Cellular Processes ◽  
Downstream Effector ◽  
Extracellular Signal ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
Selection Of

The 90 kDa ribosomal s6 kinases (RSKs) are a group of serine/threonine kinases consisting of 4 RSK isoforms (RSK1-4), of which RSK1 is also designated as p90RSK. p90RSK plays an important role in the Ras-mitogen-activated protein kinase (MAPK) signalling cascade and is the direct downstream effector of Ras-extracellular signal-regulated kinase (ERK1/2) signalling. ERK1/2 activation directly phosphorylates and activates p90RSK, which, in turn, activates various signalling events through selection of different phosphorylation substrates. Upregulation of p90RSK has been reported in numerous human diseases. p90RSK plays an important role in the regulation of diverse cellular processes. Thus, aberrant activation of p90RSK plays a critical role in the pathogenesis of organ dysfunction and damage. In this review, we focus on the current understanding of p90RSK functions and roles in the development and progression of kidney diseases. Roles of p90RSK, as well as other RSKs, in cardiovascular disorders and cancers are also discussed.

scholarly journals Phosphorylation Dynamics of JNK Signaling: Effects of Dual-Specificity Phosphatases (DUSPs) on the JNK Pathway

2019 ◽  
Vol 20 (24) ◽  
pp. 6157 ◽  
Author(s):  
Jain Ha ◽  
Eunjeong Kang ◽  
Jihye Seo ◽  
Sayeon Cho
Keyword(s):  
Inflammatory Diseases ◽  
Mitogen Activated Protein Kinase ◽  
Jnk Pathway ◽  
Jnk Signaling ◽  
Precise Control ◽  
Dual Specificity ◽  
Mitogen Activated Protein ◽  
Dual Specificity Phosphatases ◽  
Pathway Regulation ◽  
Post Modification

Protein phosphorylation affects conformational change, interaction, catalytic activity, and subcellular localization of proteins. Because the post-modification of proteins regulates diverse cellular signaling pathways, the precise control of phosphorylation states is essential for maintaining cellular homeostasis. Kinases function as phosphorylating enzymes, and phosphatases dephosphorylate their target substrates, typically in a much shorter time. The c-Jun N-terminal kinase (JNK) signaling pathway, a mitogen-activated protein kinase pathway, is regulated by a cascade of kinases and in turn regulates other physiological processes, such as cell differentiation, apoptosis, neuronal functions, and embryonic development. However, the activation of the JNK pathway is also implicated in human pathologies such as cancer, neurodegenerative diseases, and inflammatory diseases. Therefore, the proper balance between activation and inactivation of the JNK pathway needs to be tightly regulated. Dual specificity phosphatases (DUSPs) regulate the magnitude and duration of signal transduction of the JNK pathway by dephosphorylating their substrates. In this review, we will discuss the dynamics of phosphorylation/dephosphorylation, the mechanism of JNK pathway regulation by DUSPs, and the new possibilities of targeting DUSPs in JNK-related diseases elucidated in recent studies.

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