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https://www.readbyqxmd.com/read/29718933/a20-regulates-canonical-wnt-signaling-through-an-interaction-with-ripk4
#1
Brooke N Nakamura, Alison Glazier, Michael G Kattah, Bao Duong, Yanxia Jia, Daniel Campo, Ling Shao
A20 is a ubiquitin-editing enzyme that is known to regulate inflammatory signaling and cell death. However, A20 mutations are also frequently found in multiple malignancies suggesting a potential role as a tumor suppressor as well. We recently described a novel role for A20 in regulating the wnt-beta-catenin signaling pathway and suppressing colonic tumor development in mice. The underlying mechanisms for this phenomenon are unclear. To study this, we first generated A20 knockout cell lines by genome-editing techniques...
2018: PloS One
https://www.readbyqxmd.com/read/29706531/crystal-structure-of-ripk4-reveals-dimerization-dependent-kinase-activity
#2
Christine S Huang, Nina Oberbeck, Yi-Chun Hsiao, Peter Liu, Adam R Johnson, Vishva M Dixit, Sarah G Hymowitz
Receptor-interacting protein kinase 4 (RIPK4) is a highly conserved regulator of epidermal differentiation. Members of the RIPK family possess a common kinase domain as well as unique accessory domains that likely dictate subcellular localization and substrate preferences. Mutations in human RIPK4 manifest as Bartsocas-Papas syndrome (BPS), a genetic disorder characterized by severe craniofacial and limb abnormalities. We describe the structure of the murine Ripk4 (MmRipk4) kinase domain, in ATP- and inhibitor-bound forms...
April 24, 2018: Structure
https://www.readbyqxmd.com/read/29523099/novel-heterozygous-pathogenic-variants-in-chuk-in-a-patient-with-aec-like-phenotype-immune-deficiencies-and-1q21-1-microdeletion-syndrome-a-case-report
#3
Maxime Cadieux-Dion, Nicole P Safina, Kendra Engleman, Carol Saunders, Elena Repnikova, Nikita Raje, Kristi Canty, Emily Farrow, Neil Miller, Lee Zellmer, Isabelle Thiffault
BACKGROUND: Ectodermal dysplasias (ED) are a group of diseases that affects the development or function of the teeth, hair, nails and exocrine and sebaceous glands. One type of ED, ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC or Hay-Wells syndrome), is an autosomal dominant disease characterized by the presence of skin erosions affecting the palms, soles and scalp. Other clinical manifestations include ankyloblepharon filiforme adnatum, cleft lip, cleft palate, craniofacial abnormalities and ectodermal defects such as sparse wiry hair, nail changes, dental changes, and subjective hypohydrosis...
March 9, 2018: BMC Medical Genetics
https://www.readbyqxmd.com/read/29436617/ripk4-pebp1-axis-promotes-pancreatic-cancer-cell-migration-and-invasion-by-activating-raf1-mek-erk-signaling
#4
Zi-Hao Qi, Hua-Xiang Xu, Shi-Rong Zhang, Jin-Zhi Xu, Shuo Li, He-Li Gao, Wei Jin, Wen-Quan Wang, Chun-Tao Wu, Quan-Xing Ni, Xian-Jun Yu, Liang Liu
Pancreatic cancer is a lethal disease with a high metastatic potential. In our previous study, we identified a specific subgroup of patients with pancreatic cancer with a serum signature of carcinoembryonic antigen (CEA)+/cancer antigen (CA)125+/CA19-9 ≥1,000 U/ml. In this study, by using high-throughput screening analysis, we found that receptor-interacting protein kinases 4 (RIPK4) may be a key molecule involved in the high metastatic potential of this subgroup of patients with pancreatic cancer. A high RIPK4 expression predicted a poor prognosis and promoted pancreatic cancer cell migration and invasion via the RAF1/MEK/ERK pathway...
April 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29435596/ripk4-activity-in-keratinocytes-is-controlled-by-the-scf-%C3%AE-trcp-ubiquitin-ligase-to-maintain-cortical-actin-organization
#5
Giel Tanghe, Corinne Urwyler-Rösselet, Philippe De Groote, Emmanuel Dejardin, Pieter-Jan De Bock, Kris Gevaert, Peter Vandenabeele, Wim Declercq
RIPK4 is a key player in epidermal differentiation and barrier formation. RIPK4 signaling pathways controlling keratinocyte proliferation and differentiation depend on its kinase activity leading to Dvl2, Pkp1 and IRF6 phosphorylation and NF-κB activation. However, the mechanism regulating RIPK4 activity levels remains elusive. We show that cultured keratinocytes display constitutive active phosphorylated RIPK4 while PKC signaling can trigger RIPK4 activation in various non-keratinocyte cell lines, in which RIPK4 is present in a non-phosphorylated state...
February 12, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29351612/a-mutational-signature-associated-with-alcohol-consumption-and-prognostically-significantly-mutated-driver-genes-in-esophageal-squamous-cell-carcinoma
#6
X C Li, M Y Wang, M Yang, H J Dai, B F Zhang, W Wang, X L Chu, X Wang, H Zheng, R F Niu, W Zhang, K X Chen
Background: Esophageal squamous cell carcinoma (ESCC) is often diagnosed at an advanced and incurable stage. Information on driver genes and prognosticators in ESCC remains incomplete. The objective was to elucidate significantly mutated genes (SMGs), mutational signatures, and prognosticators in ESCC. Patients and Methods: Three MutSig algorithms (i.e. MutSigCV, MutSigCL and MutSigFN) and "20/20+" ratio-metric were employed to identify SMGs. Nonnegative matrix factorization was used to decipher mutational signatures...
January 16, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29317263/keratinocyte-specific-ablation-of-ripk4-allows-epidermal-cornification-but-impairs-skin-barrier-formation
#7
Corinne Urwyler-Rösselet, Giel Tanghe, Kirsten Leurs, Barbara Gilbert, Riet De Rycke, Michiel De Bruyne, Saskia Lippens, Sonia Bartunkova, Philippe De Groote, Carien Niessen, Marek Haftek, Peter Vandenabeele, Wim Declercq
In humans, receptor-interacting protein kinase 4 (RIPK4) mutations can lead to the autosomal recessive Bartsocas-Papas and popliteal pterygium syndromes, which are characterized by severe skin defects, pterygia, as well as clefting. We show here that the epithelial fusions observed in RIPK4 full knockout (KO) mice are E-cadherin dependent, as keratinocyte-specific deletion of E-cadherin in RIPK4 full KO mice rescued the tail-to-body fusion and fusion of oral epithelia. To elucidate RIPK4 function in epidermal differentiation and development, we generated epidermis-specific RIPK4 KO mice (RIPK4EKO )...
January 6, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28940926/confirmation-that-ripk4-mutations-cause-not-only-bartsocas-papas-syndrome-but-also-chand-syndrome
#8
Tiffany Busa, Mohammed Jeraiby, Alix Clémenson, Sylvie Manouvrier, Viviana Granados, Nicole Philip, Renaud Touraine
CHAND syndrome is an autosomal recessive disorder characterized by curly hair, ankyloblepharon, and nail dysplasia. Only few patients were reported to date. A homozygous RIPK4 mutation was recently identified by homozygosity mapping and whole exome sequencing in three patients from an expanded consanguineous kindred with a clinical diagnosis of CHAND syndrome. RIPK4 was previously known to be implicated in Bartsocas-Papas syndrome, the autosomal recessive form of popliteal pterygium syndrome. We report here two cases of RIPK4 homozygous mutations in a fetus with severe Bartsocas-Papas syndrome and a patient with CHAND syndrome...
September 21, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28803895/periderm-life-cycle-and-function-during-orofacial-and-epidermal-development
#9
REVIEW
Nigel L Hammond, Jill Dixon, Michael J Dixon
Development of the secondary palate involves a complex series of embryonic events which, if disrupted, result in the common congenital anomaly cleft palate. The secondary palate forms from paired palatal shelves which grow initially vertically before elevating to a horizontal position above the tongue and fusing together in the midline via the medial edge epithelia. As the epithelia of the vertical palatal shelves are in contact with the mandibular and lingual epithelia, pathological fusions between the palate and the mandible and/or the tongue must be prevented...
August 10, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28643456/irf6-expression-in-basal-epithelium-partially-rescues-irf6-knockout-mice
#10
Youssef A Kousa, Dina Moussa, Brian C Schutte
BACKGROUND: Mutations in IRF6, CHUK (IKKA), and RIPK4 can lead to a disease spectrum that includes cutaneous, limb, and craniofacial malformations. Loss of these alleles in the mouse leads to perinatal lethality and severe cutaneous, limb, and craniofacial defects also. Genetic rescue in the mouse has been shown for Ikka and Ripk4. RESULTS: Here, we show partial genetic rescue of Irf6 knockout embryos using the KRT14 promoter to drive Irf6 expression in the basal epithelium...
September 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28507225/phosphorylation-of-pkp1-by-ripk4-regulates-epidermal-differentiation-and-skin-tumorigenesis
#11
Philbert Lee, Shangwen Jiang, Yuanyuan Li, Jiping Yue, Xuewen Gou, Shao-Yu Chen, Yingming Zhao, Markus Schober, Minjia Tan, Xiaoyang Wu
Tissue homeostasis of skin is sustained by epidermal progenitor cells localized within the basal layer of the skin epithelium. Post-translational modification of the proteome, such as protein phosphorylation, plays a fundamental role in the regulation of stemness and differentiation of somatic stem cells. However, it remains unclear how phosphoproteomic changes occur and contribute to epidermal differentiation. In this study, we survey the epidermal cell differentiation in a systematic manner by combining quantitative phosphoproteomics with mammalian kinome cDNA library screen...
July 3, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28289145/interferon-regulatory-factor-6-promotes-keratinocyte-differentiation-in-response-to-porphyromonas-gingivalis
#12
Jennifer Huynh, Glen M Scholz, Jiamin Aw, Eric C Reynolds
We recently demonstrated that the expression of the interferon regulatory factor 6 (IRF6) transcription factor in oral keratinocytes was stimulated by the periodontal pathogen Porphyromonas gingivalis Here, we have established that IRF6 promotes the differentiation of oral keratinocytes in response to P. gingivalis This was evidenced by the IRF6-dependent upregulation of specific markers of keratinocyte terminal differentiation (e.g., involucrin [IVL] and keratin 13 [KRT13]), together with additional transcriptional regulators of keratinocyte differentiation, including Grainyhead-like 3 (GRHL3) and Ovo-like zinc finger 1 (OVOL1)...
May 2017: Infection and Immunity
https://www.readbyqxmd.com/read/27697098/high-level-expression-of-ripk4-and-ezh2-contributes-to-lymph-node-metastasis-and-predicts-favorable-prognosis-in-patients-with-cervical-cancer
#13
Susan Azizmohammadi, Sima Azizmohammadi, Aghdas Safari, Maria Kaghazian, Mina Sadrkhanlo, Vahid Behnod, Mehri Seifoleslami
The investigation of specific genes will establish more useful biomarkers for accurate detection and management of gynecological cancers, especially patients with cervical cancer (CCP). The aim of this study was to evaluate the expression level of RIPK4 and EZH2 messenger RNA (RIPK4 and EZH2 mRNA) in CCP. Expression of RIPK4 and EZH2 in the tissues was determined by immunohistochemistry and qRT-PCR methods. Correlations of RIPK4 and EZH2 mRNA with clinical and pathological parameters were analyzed using the Fisher's exact test...
April 14, 2017: Oncology Research
https://www.readbyqxmd.com/read/27667567/a-novel-regulatory-relationship-between-ripk4-and-elf3-in-keratinocytes
#14
Glen M Scholz, Nur S Sulaiman, Sahar Al Baiiaty, Mei Qi Kwa, Eric C Reynolds
Keratinocytes are central to the barrier functions of surface epithelia, such as the gingiva and epidermis. RIPK4 is a key regulator of keratinocyte differentiation; however, the signalling pathways in which it functions remain poorly defined. In this study, we identified a regulatory relationship between RIPK4 and ELF3, an ETS family transcription factor. RIPK4 was shown to be important for the upregulation of ELF3 gene expression by the PKC agonist PMA in both oral and epidermal keratinocytes. RIPK4 promotes keratinocyte differentiation in part by phosphorylating and thereby activating the IRF6 transcription factor...
December 2016: Cellular Signalling
https://www.readbyqxmd.com/read/27045108/synthetic-biology-reveals-the-uniqueness-of-the-rip-kinase-domain
#15
Steven M Chirieleison, Sylvia B Kertesy, Derek W Abbott
The RIP kinases (RIPKs) play an essential role in inflammatory signaling and inflammatory cell death. However, the function of their kinase activity has been enigmatic, and only recently has kinase domain activity been shown to be crucial for their signal transduction capacity. Despite this uncertainty, the RIPKs have been the subject of intense pharmaceutical development with a number of compounds currently in preclinical testing. In this work, we seek to determine the functional redundancy between the kinase domains of the four major RIPK family members...
May 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27014863/ripk4-activates-an-irf6-mediated-proinflammatory-cytokine-response-in-keratinocytes
#16
Mei Qi Kwa, Glen M Scholz, Eric C Reynolds
Keratinocytes of the oral mucosa and epidermis play key roles in host defense. In addition to functioning as a physical barrier, they also produce cytokines to elicit inflammation in response to infection or injury. We recently established that receptor-interacting protein kinase 4 (RIPK4) and interferon regulatory factor 6 (IRF6) function as a cell-intrinsic signaling axis to regulate keratinocyte differentiation. In this study, we have demonstrated a functional relationship between RIPK4 and IRF6 in the control of proinflammatory cytokine expression in keratinocytes...
July 2016: Cytokine
https://www.readbyqxmd.com/read/26972000/substrate-trapped-interactors-of-phd3-and-fih-cluster-in-distinct-signaling-pathways
#17
Javier Rodriguez, Ruth Pilkington, Amaya Garcia Munoz, Lan K Nguyen, Nora Rauch, Susan Kennedy, Naser Monsefi, Ana Herrero, Cormac T Taylor, Alex von Kriegsheim
Amino acid hydroxylation is a post-translational modification that regulates intra- and inter-molecular protein-protein interactions. The modifications are regulated by a family of 2-oxoglutarate- (2OG) dependent enzymes and, although the biochemistry is well understood, until now only a few substrates have been described for these enzymes. Using quantitative interaction proteomics, we screened for substrates of the proline hydroxylase PHD3 and the asparagine hydroxylase FIH, which regulate the HIF-mediated hypoxic response...
March 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/26616804/-association-between-ripk4-relative-copy-number-and-prognosis-of-colorectal-cancer-patient-after-oxaliplatin-based-chemotherapy
#18
Kangsheng Peng, Moubin Lin, Qing Wei, Huaguang Li, Chenbo Zhang, Ruting Xie, Zhanju Liu
OBJECTIVE: To investigate the association between receptor-interacting kinase protein 4 (RIPK4) relative copy number (RCN) and prognosis of stage III( colorectal cancer (CRC) patients treated with oxaliplatin-based chemotherapy. METHODS: RIPK4 RCN was determined by real-time PCR and then dichotomized into high RIPK4 RCN group(n=35) and low RIPK4 RCN group (n=104) using the third quartile as the cut-off point. Overall survival (OS) and recurrence-free survival (RFS) were compared between high and low RIPK4 RCN groups...
November 2015: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/26522402/changes-in-markers-associated-with-dendritic-cells-driving%C3%A2-the-differentiation-of-either-th2-cells-or-regulatory%C3%A2-t%C3%A2-cells-correlate-with-clinical-benefit-during-allergen-immunotherapy
#19
Claire Gueguen, Julien Bouley, Hélène Moussu, Sonia Luce, Magalie Duchateau, Julia Chamot-Rooke, Marc Pallardy, Vincent Lombardi, Emmanuel Nony, Véronique Baron-Bodo, Laurent Mascarell, Philippe Moingeon
BACKGROUND: Regulatory dendritic cell (DC) markers, such as C1Q, are upregulated in PBMCs of patients with grass pollen allergy exhibiting clinical benefit during allergen immunotherapy (AIT). OBJECTIVES: We sought to define markers differentially expressed in human monocyte-derived DCs differentiated toward a proallergic (DCs driving the differentiation of TH2 cells [DC2s]) phenotype and investigate whether changes in such markers in the blood correlate with AIT efficacy...
February 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/26148476/increased-ripk4-expression-is-associated-with-progression-and-poor-prognosis-in-cervical-squamous-cell-carcinoma-patients
#20
De-Qing Liu, Fang-Fang Li, Jiang-Bo Zhang, Tie-Jun Zhou, Wen-Qiong Xue, Xiao-Hui Zheng, Yuan-Bin Chen, Xiao-Yu Liao, Lan Zhang, Shao-Dan Zhang, Ye-Zhu Hu, Wei-Hua Jia
Aberrant expression of receptor interacting protein kinase 4 (RIPK4), a crucial regulatory protein of Wnt/β-catenin signaling, has recently been reported to be involved in several cancers. Here, we report the potential clinical implication and biological functions of RIPK4 in cervical squamous cell carcinoma (CSCC). One hundred and ninety-eight CSCC cases, 109 low-grade squamous intraepithelial lesions (LSILs), 141 high-grade squamous intraepithelial lesions (HSILs) and 63 chronic cervicitis were collected...
2015: Scientific Reports
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