scholarly journals PKCα/ERK/C7ORF41 axis regulates epidermal keratinocyte differentiation through the IKKα nuclear translocation

2021 ◽  
Vol 478 (4) ◽  
pp. 839-854
Author(s):  
Feng-Juan Yan ◽  
Yong-Jian Wang ◽  
Song-En Wang ◽  
Hai-Ting Hong
Keyword(s):  
Signaling Pathway ◽  
Molecular Basis ◽  
Skin Diseases ◽  
Nuclear Translocation ◽  
Skin Barrier ◽  
Tissue Microarrays ◽  
Erk Signaling ◽  
Keratinocyte Differentiation ◽  
Hacat Keratinocytes

Aberrant differentiation of keratinocytes disrupts the skin barrier and causes a series of skin diseases. However, the molecular basis of keratinocyte differentiation is still poorly understood. In the present study, we examined the expression of C7ORF41 using tissue microarrays by immunohistochemistry and found that C7ORF41 is specifically expressed in the basal layers of skin epithelium and its expression is gradually decreased during keratinocytes differentiation. Importantly, we corroborated the pivotal role of C7ORF41 during keratinocyte differentiation by C7ORF41 knockdown or overexpression in TPA-induced Hacat keratinocytes. Mechanismly, we first demonstrated that C7ORF41 inhibited keratinocyte differentiation mainly through formatting a complex with IKKα in the cytoplasm, which thus blocked the nuclear translocation of IKKα. Furthermore, we also demonstrated that inhibiting the PKCα/ERK signaling pathway reversed the reduction in C7ORF41 in TPA-induced keratinocytes, indicating that C7ORF41 expression could be regulated by upstream PKCα/ERK signaling pathway during keratinocyte differentiation. Collectively, our study uncovers a novel regulatory network PKCα/ERK/C7ORF41/IKKα during keratinocyte differentiation, which provides potential therapeutic targets for skin diseases.

Role of testosterone in regulating induction of TNF-α in rat spleen via ERK signaling pathway

Steroids ◽  
2016 ◽  
Vol 111 ◽  
pp. 148-154 ◽  
Author(s):  
Chien-Wei Chen ◽  
Cai-Yun Jian ◽  
Po-Han Lin ◽  
Chih-Chieh Chen ◽  
Fu-Kong Lieu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Erk Signaling ◽  
Tnf Α

scholarly journals Cellular DNAJA3, a Novel VP1-Interacting Protein, Inhibits Foot-and-Mouth Disease Virus Replication by Inducing Lysosomal Degradation of VP1 and Attenuating Its Antagonistic Role in the Beta Interferon Signaling Pathway

2019 ◽  
Vol 93 (13) ◽  
Author(s):  
Wei Zhang ◽  
Fan Yang ◽  
Zixiang Zhu ◽  
Yang Yang ◽  
Zhifang Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Disease Virus ◽  
Nuclear Translocation ◽  
Foot And Mouth Disease ◽  
Lysosomal Degradation ◽  
Beta Interferon ◽  
Mouth Disease Virus ◽  
Antiviral Role ◽  
Fmdv Replication

ABSTRACTDnaJ heat shock protein family (Hsp40) member A3 (DNAJA3) plays an important role in viral infections. However, the role of DNAJA3 in replication of foot-and-mouth-disease virus (FMDV) remains unknown. In this study, DNAJA3, a novel binding partner of VP1, was identified using yeast two-hybrid screening. The DNAJA3-VP1 interaction was further confirmed by coimmunoprecipitation and colocalization in FMDV-infected cells. The J domain of DNAJA3 (amino acids 1 to 168) and the lysine at position 208 (K208) of VP1 were shown to be critical for the DNAJA3-VP1 interaction. Overexpression of DNAJA3 dramatically dampened FMDV replication, whereas loss of function of DNAJA3 elicited opposing effects against FMDV replication. Mechanistical study demonstrated that K208 of VP1 was critical for reducing virus titer caused by DNAJA3 using K208A mutant virus. DNAJA3 induced lysosomal degradation of VP1 by interacting with LC3 to enhance the activation of lysosomal pathway. Meanwhile, we discovered that VP1 suppressed the beta interferon (IFN-β) signaling pathway by inhibiting the phosphorylation, dimerization, and nuclear translocation of IRF3. This inhibitory effect was considerably boosted in DNAJA3-knockout cells. In contrast, overexpression of DNAJA3 markedly attenuated VP1-mediated suppression on the IFN-β signaling pathway. Poly(I⋅C)-induced phosphorylation of IRF3 was also decreased in DNAJA3-knockout cells compared to that in the DNAJA3-WT cells. In conclusion, our study described a novel role for DNAJA3 in the host’s antiviral response by inducing the lysosomal degradation of VP1 and attenuating the VP1-induced suppressive effect on the IFN-β signaling pathway.IMPORTANCEThis study pioneeringly determined the antiviral role of DNAJA3 in FMDV. DNAJA3 was found to interact with FMDV VP1 and trigger its degradation via the lysosomal pathway. In addition, this study is also the first to clarify the mechanism by which VP1 suppressed IFN-β signaling pathway by inhibiting the phosphorylation, dimerization, and nuclear translocation of IRF3. Moreover, DNAJA3 significantly abrogated VP1-induced inhibitive effect on the IFN-β signaling pathway. These data suggested that DNAJA3 plays an important antiviral role against FMDV by both degrading VP1 and restoring of IFN-β signaling pathway.

The role of β-HCG and VEGF-MEK/ERK signaling pathway in villi angiogenesis in patients with missed abortion

Placenta ◽  
2021 ◽  
Vol 103 ◽  
pp. 16-23
Author(s):  
Guangzhuang Jing ◽  
Jianling Yao ◽  
Yuhui Dang ◽  
Weitao Liang ◽  
Li'ao Xie ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Erk Signaling ◽  
Missed Abortion ◽  
Β Hcg

Potential role of andrographolide in the proliferation of osteoblasts mediated by the ERK signaling pathway

2016 ◽  
Vol 83 ◽  
pp. 1335-1344 ◽  
Author(s):  
Bo Li ◽  
Ru-Yin Hu ◽  
Li Sun ◽  
Rui Luo ◽  
Kai-Hang Lu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Potential Role ◽  
Erk Signaling

scholarly journals From Peripheral to Central: The Role of ERK Signaling Pathway in Acupuncture Analgesia

2014 ◽  
Vol 15 (5) ◽  
pp. 535-549 ◽  
Author(s):  
Ji-Yeun Park ◽  
Jongbae J. Park ◽  
Songhee Jeon ◽  
Ah-Reum Doo ◽  
Seung-Nam Kim ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Erk Signaling ◽  
Acupuncture Analgesia

scholarly journals OR20-01 AMH Preserves Fertility in Chemotherapy-Treated Mice Through a Mechanism Involving Autophagy

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Isabelle Beau ◽  
Charlotte Sonigo ◽  
Nadine Binart
Keyword(s):  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Alkylating Agents ◽  
Phosphatidyl Inositol ◽  
Autophagic Flux ◽  
Pi3k Signaling ◽  
Primordial Follicles ◽  
Pi3k Signaling Pathway

Abstract Chemotherapy-induced ovarian failure and infertility is an important concern in female cancer patients. The follicular ovarian reserve is established early in life then keeps declining regularly along reproductive life. This reserve is constituted by dormant primordial follicles (PMF) which are necessary to maintain female reproductive function. There is a continuous repression of PMF activation in early growing follicle through the balance between factors activating the initiation of follicular growth, mainly actors of the phosphatidyl-inositol-3-kinase (PI3K) signaling pathway, and inhibiting factors such as Anti-Müllerian Hormone (AMH). Any alteration of this equilibrium may induce early follicle depletion and subsequent infertility. Cyclophosphamide (Cy) one of the alkylating agents commonly used for treating breast cancer is able to trigger PMF activation further leading to premature ovarian insufficiency. Preventing chemotherapy-induced ovarian dysfunction might represent an option for preserving optimal chances of natural or medically assisted conceptions after healing. We showed in a model of Cy-treated pubertal mice, that AMH administration was able to restrain PMF depletion by counting the total PMF number within mouse ovaries. Moreover, the PI3K signaling pathway was evaluated following Cy administration with and without AMH injection. We showed that AMH decreased the phosphorylation of FOXO3A, a transcription factor of PMF activation and induced its nuclear translocation. Altogether, the results support a protective role of AMH against Cy-induced follicular loss. To better understand AMH action in the ovary, we investigated the molecular mechanism to explain the protective effect of this hormone on the PMF pool. It has been reported that autophagy, a lysosomal degradative ubiquitous process implicated in cellular homeostasis, was involved in both ovarian follicular death and survival mostly by PI3K pathway (Gawriluk et al. Reproduction 2011 141, 759–765). We show in mice that Cy inhibits autophagy in the ovary while AMH induces autophagy. In vivo analysis of autophagic flux is currently in progress to dissect this process more finely. Interestingly, FOXO3A was shown to be related to autophagy activation. To investigate the role of FOXO3A in AMH-induced autophagy further, we analyzed mRNA and protein expression of autophagy-related genes controlled by FOXO3A, including BECLIN-1, ATG12, ULK1, BNIP3, GABARAP, and LC3B. These findings establish a close relationship between AMH and autophagy to protect PMF stockpile and to limit follicular depletion induced by Cy.

The Therapeutic Potential of MAPK/ERK Inhibitors in the Treatment of Colorectal Cancer

2021 ◽  
Vol 21 ◽  
Author(s):  
Mehran Pashirzad ◽  
Reihaneh Khorasanian ◽  
Maryam Mahmoudi Fard ◽  
Mohammad-Hassan Arjmand ◽  
Hadis Langari ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Erk Signaling ◽  
Clinical Settings ◽  
Cancer Cell Proliferation ◽  
Resistance Mutations ◽  
Clinical Value

: The MAPK/ERK signaling pathway regulates cancer cell proliferation, apoptosis, inflammation, angiogenesis, metastasis and drug resistance. Mutations and up-regulation of components of the MAPK/ERK signaling pathway, as well as over-activation of this critical signaling pathway, are frequently observed in colorectal carcinomas. Targeting the MAPK/ERK signaling pathway, using specific pharmacological inhibitors, elicits potent anti-tumor effects, supporting the therapeutic potential of these inhibitors in the treatment of CRC. Several drugs have recently been developed for the inhibition of the MEK/ERK pathway in preclinical and clinical settings, such as MEK162 and MK-2206. MEK1/2 inhibitors demonstrate promising efficacy and anticancer activity for the treatment of this malignancy. This review summarizes the current knowledge on the role of the MAPK/ERK signaling pathway in the pathogenesis of CRC and the potential clinical value of synthetic inhibitors of this pathway in preventing CRC progression for a better understanding, and hence, better management of colorectal cancer.

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