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Kibra

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https://www.readbyqxmd.com/read/29724824/distinctive-phosphoinositide-and-ca-2-binding-properties-of-normal-and-cognitive-performance-linked-variant-forms-of-kibra-c2-domain
#1
Mareike G Posner, Abhishek Upadhyay, Rieko Ishima, Antreas C Kalli, Gemma Harris, Joachim Kremerskothen, Mark S P Sansom, Susan J Crennell, Stefan Bagby
KIBRA, a multi-functional scaffold protein with around twenty known binding partners, is involved in memory and cognition, organ size control via the Hippo pathway, cell polarity, and membrane trafficking. KIBRA includes tandem N-terminal WW domains, a C2 domain and motifs for binding aPKC and PDZ domains. A naturally occurring human KIBRA variant involving residue changes at positions 734 (M-to-I) and 735 (S-to-A) within the C2 domain affects cognitive performance. We have elucidated 3D structures, and calcium and phosphoinositide binding properties, of human KIBRA C2 domain...
May 3, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29659170/association-of-peripheral-blood-leukocyte-kibra-methylation-with-gastric-cancer-risk-a-case-control-study
#2
Yan Zhang, Haibo Zhou, Hongxu Sun, Jie Chen, Di Huang, Xu Han, Xiyun Ren, Shangqun Lin, Qing Fan, Wenjing Tian, Yashuang Zhao
KIBRA was reported to be involved in various types of cancer and can be detected in blood. The purpose of this study was to investigate the relationship between the status of KIBRA methylation in peripheral blood leukocytes and gastric cancer (GC) risk. A case-control study was carried out to evaluate the association of blood cell-derived KIBRA methylation with the risk of GC using methylation-sensitive high-resolution melting analysis. A total of 393 cases and 393 controls were detected, respectively. Compared with the subjects in the KIBRA negative methylation (NM) group, positive methylation (PM) subjects exhibited a 1...
April 16, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29562176/kibra-wwc1-is-a-metastasis-suppressor-gene-affected-by-chromosome-5q-loss-in-triple-negative-breast-cancer
#3
Jennifer F Knight, Vanessa Y C Sung, Elena Kuzmin, Amber L Couzens, Danielle A de Verteuil, Colin D H Ratcliffe, Paula P Coelho, Radia M Johnson, Payman Samavarchi-Tehrani, Tina Gruosso, Harvey W Smith, Wontae Lee, Sadiq M Saleh, Dongmei Zuo, Hong Zhao, Marie-Christine Guiot, Ryan R Davis, Jeffrey P Gregg, Christopher Moraes, Anne-Claude Gingras, Morag Park
Triple-negative breast cancers (TNBCs) display a complex spectrum of mutations and chromosomal aberrations. Chromosome 5q (5q) loss is detected in up to 70% of TNBCs, but little is known regarding the genetic drivers associated with this event. Here, we show somatic deletion of a region syntenic with human 5q33.2-35.3 in a mouse model of TNBC. Mechanistically, we identify KIBRA as a major factor contributing to the effects of 5q loss on tumor growth and metastatic progression. Re-expression of KIBRA impairs metastasis in vivo and inhibits tumorsphere formation by TNBC cells in vitro...
March 20, 2018: Cell Reports
https://www.readbyqxmd.com/read/29555977/epigenetic-restriction-of-hippo-signaling-by-morc2-underlies-stemness-of-hepatocellular-carcinoma-cells
#4
Tao Wang, Zhong-Yi Qin, Liang-Zhi Wen, Yan Guo, Qin Liu, Zeng-Jie Lei, Wei Pan, Kai-Jun Liu, Xing-Wei Wang, Shu-Jie Lai, Wen-Jing Sun, Yan-Ling Wei, Lei Liu, Ling Guo, Yu-Qin Chen, Jun Wang, Hua-Liang Xiao, Xiu-Wu Bian, Dong-Feng Chen, Bin Wang
The evolutionarily conserved Hippo signaling pathway is a key regulator of stem cell self-renewal, differentiation, and organ size. While alterations in Hippo signaling are causally linked to uncontrolled cell growth and a broad range of malignancies, genetic mutations in the Hippo pathway are uncommon and it is unclear how the tumor suppressor function of the Hippo pathway is disrupted in human cancers. Here, we report a novel epigenetic mechanism of Hippo inactivation in the context of hepatocellular carcinoma (HCC)...
March 19, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29526515/unique-expression-pattern-of-kibra-in-the-enteric-nervous-system-of-app-ps1-mice
#5
Jianli Feng, Lingling Dong, Jing Zhang, Xiaolei Han, Shi Tang, Lin Song, Lin Cong, Xiang Wang, Yongxiang Wang, Yifeng Du
KIBRA has been recognized as a memory-related gene, which is abundant in the brain and kidney of mammals. However, the expression pattern of KIBRA in the "second brain"-enteric nervous system (ENS) is still unknown, especially in neurodegenerative disorders. In this study, we aimed to investigate the detailed expression pattern of KIBRA in the intestinal myenteric nerve plexus of APP/PS1 and wild type mice by whole mount staining technology. The deposition of Aβ and increased levels of phosphorylated Tau (p-Tau) and total Tau (T-Tau) protein were observed in the intestinal myenteric nerve plexus of APP/PS1 mice...
May 14, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29523820/zfp226-is-a-novel-artificial-transcription-factor-for-selective-activation-of-tumor-suppressor-kibra
#6
Katrin Schelleckes, Boris Schmitz, Malte Lenders, Mirja Mewes, Stefan-Martin Brand, Eva Brand
KIBRA has been suggested as a key regulator of the hippo pathway, regulating organ size, cell contact inhibition as well as tissue regeneration and tumorigenesis. Recently, alterations of KIBRA expression caused by promotor methylation have been reported for several types of cancer. Our current study aimed to design an artificial transcription factor capable of re-activating expression of the tumor suppressor KIBRA and the hippo pathway. We engineered a new gene named 'ZFP226' encoding for a ~23 kDa fusion protein...
March 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29477107/evolution-of-mechanotransduction-via-yap-taz-in-animal-epithelia
#7
REVIEW
Ahmed Elbediwy, Barry J Thompson
Mechanical stretch forces can control the growth of epithelial tissues such as mammalian skin, whose surface area is precisely coordinated with body size. In skin keratinocytes cultured in vitro, mechanical forces acting via Integrin adhesions and the actin cytoskeleton have been shown to induce nuclear translocation of YAP/TAZ co-activators to induce cell proliferation. Furthermore, conditional knockouts of both YAP (also called YAP1) and TAZ (also called WWTR1) in mouse skin resemble the phenotype of skin-specific loss of Integrin beta1 (ITGB1), indicating that this signalling mechanism is important in vivo...
February 21, 2018: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/29416687/no-differences-in-brain-microstructure-between-young-kibra-c-carriers-and-non-carriers
#8
Li Hu, Qunxing Xu, Jizhen Li, Feifei Wang, Xinghua Xu, Zhiyuan Sun, Xiangxing Ma, Yong Liu, Qing Wang, Dawei Wang
KIBRA rs17070145 polymorphism is associated with variations in memory function and the microstructure of related brain areas. Diffusion kurtosis imaging (DKI) as an extension of diffusion tensor imaging that can provide more information about changes in microstructure, based on the idea that water diffusion in biological tissues is heterogeneous due to structural hindrance and restriction. We used DKI to explore the relationship between KIBRA gene polymorphism and brain microstructure in young adults. We recruited 100 healthy young volunteers, including 53 TT carriers and 47 C allele carriers...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29391469/kibra-is-associated-with-accelerated-cognitive-decline-and-hippocampal-atrophy-in-apoe-%C3%AE%C2%B54-positive-cognitively-normal-adults-with-high-a%C3%AE-amyloid-burden
#9
Tenielle Porter, Samantha C Burnham, Vincent Doré, Greg Savage, Pierrick Bourgeat, Kimberly Begemann, Lidija Milicic, David Ames, Ashley I Bush, Paul Maruff, Colin L Masters, Christopher C Rowe, Stephanie Rainey-Smith, Ralph N Martins, David Groth, Giuseppe Verdile, Victor L Villemagne, Simon M Laws
A single nucleotide polymorphism, rs17070145, in the KIdney and BRAin expressed protein (KIBRA) gene has been associated with cognition and hippocampal volume in cognitively normal (CN) individuals. However, the impact of rs17070145 on longitudinal cognitive decline and hippocampal atrophy in CN adults at greatest risk of developing Alzheimer's disease is unknown. We investigated the impact rs17070145 has on the rate of cognitive decline and hippocampal atrophy over six years in 602 CN adults, with known brain Aβ-amyloid levels and whether there is an interactive effect with APOE genotype...
February 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29046731/promoter-methylation-inhibits-expression-of-tumor-suppressor-kibra-in-human-clear-cell-renal-cell-carcinoma
#10
Katrin Schelleckes, Boris Schmitz, Giuliano Ciarimboli, Malte Lenders, Hermann J Pavenstädt, Edwin Herrmann, Stefan-Martin Brand, Eva Brand
BACKGROUND: KIBRA has been suggested as a key regulator of the Hippo signaling pathway, regulating organ size, cell contact inhibition, tissue regeneration as well as tumorigenesis and cystogenesis. We recently reported that human KIBRA expression depends on a complex alternative CpG-rich promoter system. Our current study aimed at the identification of epigenetic mechanisms associated with alterations in KIBRA expression regulation. RESULTS: We identified two separated methylation-sensitive CpG islands located to independent KIBRA promoter regions...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/29032191/aging-and-a-genetic-kibra-polymorphism-interactively-affect-feedback-and-observation-based-probabilistic-classification-learning
#11
Nicolas W Schuck, Jessica R Petok, Martijn Meeter, Brit-Maren M Schjeide, Julia Schröder, Lars Bertram, Mark A Gluck, Shu-Chen Li
Probabilistic category learning involves complex interactions between the hippocampus and striatum that may depend on whether acquisition occurs via feedback or observation. Little is known about how healthy aging affects these processes. We tested whether age-related behavioral differences in probabilistic category learning from feedback or observation depend on a genetic factor known to influence individual differences in hippocampal function, the KIBRA gene (single nucleotide polymorphism rs17070145). Results showed comparable age-related performance impairments in observational as well as feedback-based learning...
January 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29017577/elevated-expression-of-par3-promotes-prostate-cancer-metastasis-by-forming-a-par3-apkc-kibra-complex-and-inactivating-the-hippo-pathway
#12
Pei-Jie Zhou, Wei Xue, Jinliang Peng, Yanqing Wang, Lianzi Wei, Ziqiang Yang, Helen He Zhu, Yu-Xiang Fang, Wei-Qiang Gao
BACKGROUND: Prostate cancer (PCa) is one of the most frequent tumors and leading cause of cancer deaths among males worldwide. The majority of deaths are due to recurrence and subsequent development of the metastatic cancer. Although loss or dislocalization of polarity proteins has been implicated in embryogenesis deficiency and tumorigenesis, association of polarity protein expression levels with tumor metastasis remains unclear. METHODS: Bioinformatics, qRT-PCR, western blot and immunohistochemical (IHC) analyses were used to examine expression of Par3, a key component of polarity-associated partitioning defective (PAR) complex, in primary and metastatic clinical PCa samples...
October 10, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28982981/the-hippo-pathway-regulator-kibra-promotes-podocyte-injury-by-inhibiting-yap-signaling-and-disrupting-actin-cytoskeletal-dynamics
#13
Kristin Meliambro, Jenny S Wong, Justina Ray, Rhodora C Calizo, Sara Towne, Beatriz Cole, Fadi El Salem, Ronald E Gordon, Lewis Kaufman, John C He, Evren U Azeloglu, Kirk N Campbell
Kidney podocytes represent a key constituent of the glomerular filtration barrier. Identifying the molecular mechanisms of podocyte injury and survival is important for better understanding and management of kidney diseases. KIBRA (<u>ki</u>dney <u>bra</u>in protein), an upstream regulator of the Hippo signaling pathway encoded by the Wwc1 gene, shares the pro-injury properties of its putative binding partner dendrin and antagonizes the pro-survival signaling of the downstream Hippo pathway effector YAP (Yes-associated protein) in Drosophila and MCF10A cells...
December 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28859866/association-of-kibra-polymorphism-with-risk-of-alzheimer-s-disease-evidence-based-on-20-case-control-studies
#14
Junjun Ling, Yi Huang, Liang Zhang, Dongfeng Wei, Weidong Cheng
Kidney and brain expressed protein (KIBRA) has been demonstrated to play an important role in episodic memory by genome-wide association study (GWAS). Since memory impairment is a typical clinical feature of AD, KIBRA has been considered to be a candidate gene for AD. Previous case-control association studies on KIBRA SNP rs17070145 have yielded inconsistent results. Thus, this study aimed to assess the risk of KIBRA polymorphism for sporadic AD via meta-analysis. A total of 7 articles including 20 case-control studies were included in this study...
August 30, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28815883/wwc2-is-an-independent-prognostic-factor-and-prevents-invasion-via-hippo-signalling-in-hepatocellular-carcinoma
#15
Yijun Zhang, Shumei Yan, Jiewei Chen, Caixia Gan, Dong Chen, Yan Li, Jiahuai Wen, Joachim Kremerskothen, Shilu Chen, Jiangbo Zhang, Yun Cao
WWC family proteins negatively regulate HEK293 cell proliferation and organ growth by suppressing the transcriptional activity of Yes-associated protein (YAP), a major effector of the Hippo pathway. The function of the scaffolding protein WWC1 (also called KIBRA) has been intensively studied in cells and animal models. However, the expression and clinicopathologic significance of WWC2 in cancer are poorly characterized. This study aimed to clarify the biological function and mechanism of action of WWC2 in hepatocellular carcinoma (HCC)...
December 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28720576/deubiquitinating-enzyme-usp9x-suppresses-tumor-growth-via-lats-kinase-and-core-components-of-the-hippo-pathway
#16
Aleksandra Toloczko, Fusheng Guo, Hiu-Fung Yuen, Qing Wen, Stephen A Wood, Yan Shan Ong, Pei Yi Chan, Asfa Alli Shaik, Jayantha Gunaratne, Mark J Dunne, Wanjin Hong, Siew Wee Chan
The core LATS kinases of the Hippo tumor suppressor pathway phosphorylate and inhibit the downstream transcriptional co-activators YAP and TAZ, which are implicated in various cancers. Recent studies have identified various E3 ubiquitin ligases that negatively regulate the Hippo pathway via ubiquitination, yet few deubiquitinating enzymes (DUB) have been implicated. In this study, we report the DUB USP9X is an important regulator of the core kinases of this pathway. USP9X interacted strongly with LATS kinase and to a lesser extent with WW45, KIBRA, and Angiomotin, and LATS co-migrated exclusively with USP9X during gel filtration chromatography analysis...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28664913/kibra-attains-oncogenic-activity-by-repressing-rassf1a
#17
Anuj, Lakshmi Arivazhagan, Rohan Prasad Surabhi, Archana Kanakarajan, Sandhya Sundaram, Ravi Shankar Pitani, Lakmini Mudduwa, Joachim Kremerskothen, Ganesh Venkatraman, Suresh K Rayala
BACKGROUND: KIBRA-initially identified as a neuronal associated protein is now shown to be functionally associated with other tissue types as well. KIBRA interacts with dyenin light chain 1 and this interaction is essential for oestrogen receptor transactivation in breast cancer cells. KIBRA as a substrate of Cdk1, Aurora kinase and ERK plays an important role in regulating cell cycle, cell proliferation and migration. Despite these evidences, the exact role of KIBRA in cancer progression is not known...
June 29, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28648820/selective-erasure-of-distinct-forms-of-long-term-synaptic-plasticity-underlying-different-forms-of-memory-in-the-same-postsynaptic-neuron
#18
Jiangyuan Hu, Larissa Ferguson, Kerry Adler, Carole A Farah, Margaret H Hastings, Wayne S Sossin, Samuel Schacher
Generalization of fear responses to non-threatening stimuli is a feature of anxiety disorders. It has been challenging to target maladaptive generalized memories without affecting adaptive memories. Synapse-specific long-term plasticity underlying memory involves the targeting of plasticity-related proteins (PRPs) to activated synapses. If distinct tags and PRPs are used for different forms of plasticity, one could selectively remove distinct forms of memory. Using a stimulation paradigm in which associative long-term facilitation (LTF) occurs at one input and non-associative LTF at another input to the same postsynaptic neuron in an Aplysia sensorimotor preparation, we found that each form of LTF is reversed by inhibiting distinct isoforms of protein kinase M (PKM), putative PRPs, in the postsynaptic neuron...
July 10, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28380666/whole-transcriptome-profiling-of-the-human-hippocampus-suggests-an-involvement-of-the-kibra-rs17070145-polymorphism-in-differential-activation-of-the-mapk-signaling-pathway
#19
Ignazio S Piras, Jonida Krate, Isabelle Schrauwen, Jason J Corneveaux, Geidy E Serrano, Lucia Sue, Thomas G Beach, Matthew J Huentelman
The rs17070145-T variant of the WWC1 gene, coding for the KIBRA protein, has been associated with both increased episodic memory performance and lowered risk for late onset Alzheimer's disease, although the mechanism behind this protective effect has not been completely elucidated. To achieve a better understanding of the pathways modulated by rs17070145 and its associated functional variant(s), we used laser capture microdissection (LCM) and RNA-sequencing to investigate the effect of rs17070145 genotypes on whole transcriptome expression in the human hippocampus (HP) of 22 neuropathologically normal individuals, with a specific focus on the dentate gyrus (DG) and at the pyramidal cells (PC) of CA1 and CA3 sub-regions...
July 2017: Hippocampus
https://www.readbyqxmd.com/read/28292426/kibra-and-merlin-activate-the-hippo-pathway-spatially-distinct-from-and-independent-of-expanded
#20
Ting Su, Michael Z Ludwig, Jiajie Xu, Richard G Fehon
The Hippo pathway is emerging as a key evolutionarily conserved signaling mechanism that controls organ size. Three membrane-associated proteins, Kibra, Merlin, and Expanded, regulate pathway activity, but the precise molecular mechanism by which they function is still poorly understood. Here we provide evidence that Merlin and Kibra activate Hippo signaling in parallel to Expanded at a spatially distinct cellular domain, the medial apical cortex. Merlin and Kibra together recruit the adapter protein Salvador, which in turn recruits the core kinase Hippo...
March 13, 2017: Developmental Cell
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