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https://www.readbyqxmd.com/read/29046731/promoter-methylation-inhibits-expression-of-tumor-suppressor-kibra-in-human-clear-cell-renal-cell-carcinoma
#1
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
#2
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...
September 5, 2017: 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
#3
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
#4
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 (KIdney BRAin 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...
October 5, 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
#5
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
#6
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)...
August 16, 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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28079891/crb3-regulates-contact-inhibition-by-activating-the-hippo-pathway-in-mammary-epithelial-cells
#12
Xiaona Mao, Pingping Li, Yaochun Wang, Zheyong Liang, Jie Liu, Juan Li, Yina Jiang, Gang Bao, Lei Li, Bofeng Zhu, Yu Ren, Xinhan Zhao, Jianmin Zhang, Yu Liu, Jin Yang, Peijun Liu
The loss of contact inhibition is a hallmark of cancer cells. The Hippo pathway has recently been shown to be an important regulator of contact inhibition, and the cell apical polarity determinant protein CRB3 has been suggested to be involved in Hippo signalling. However, whether CRB3 regulates contact inhibition in mammary cells remains unclear, and the underlying mechanisms have not been elucidated. As shown in the present study, CRB3 decreases cell proliferation, promotes apoptosis, and enhances the formation of tight and adherens junctions...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/27620974/apoe-and-kibra-interactions-on-brain-functional-connectivity-in-healthy-young-adults
#13
Ningnannan Zhang, Huaigui Liu, Wen Qin, Bing Liu, Tianzi Jiang, Chunshui Yu
Genetic variations of APOE and KIBRA have been associated with human memory and Alzheimer's disease. APOE and KIBRA can jointly modulate glutamate receptor to influence long-term potentiation; however, their interactions on brain functional connectivity remain unknown. Here, we investigated additive and epistatic interactions between APOE and KIBRA (rs17070145) on brain functional connectivity density (FCD) in 267 healthy young adults. A voxel-based FCD analysis was performed to identify brain regions with significant APOE-KIBRA interaction...
October 1, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/27498008/the-memory-gene-kibra-is-a-bidirectional-regulator-of-synaptic-and-structural-plasticity-in-the-adult-brain
#14
Fabrice D Heitz, Mélissa Farinelli, Safa Mohanna, Martin Kahn, Kerstin Duning, Marco C Frey, Hermann Pavenstädt, Isabelle M Mansuy
Memory formation is associated with activity-dependent changes in synaptic plasticity. The mechanisms underlying these processes are complex and involve multiple components. Recent work has implicated the protein KIBRA in human memory, but its molecular functions in memory processes remain not fully understood. Here, we show that a selective overexpression of KIBRA in neurons increases hippocampal long-term potentiation (LTP) but prevents the induction of long-term depression (LTD), and impairs spatial long-term memory in adult mice...
November 2016: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/27240404/the-regulatory-role-of-kibra-and-ptpn14-in-hippo-signaling-and-beyond
#15
REVIEW
Kayla E Wilson, Nuo Yang, Ashley L Mussell, Jianmin Zhang
The Hippo signaling pathway regulates cellular proliferation and survival, thus exerting profound effects on normal cell fate and tumorigenesis. Pivotal effectors of this pathway are YAP/TAZ, transcriptional co-activators whose dysfunction contributes to the development of cancer. Complex networks of intracellular and extracellular signaling pathways that modulate YAP and TAZ activities have recently been identified. Among them, KIBRA and PTPN14 are two evolutionarily-conserved and important YAP/TAZ upstream regulators...
2016: Genes
https://www.readbyqxmd.com/read/27220053/kibra-promotes-prostate-cancer-cell-proliferation-and-motility
#16
EDITORIAL
Seth Stauffer, Xingcheng Chen, Lin Zhang, Yuanhong Chen, Jixin Dong
KIBRA is a regulator of the Hippo-yes-associated protein (YAP) pathway, which plays a critical role in tumorigenesis. In the present study, we show that KIBRA is a positive regulator in prostate cancer cell proliferation and motility. We found that KIBRA is transcriptionally upregulated in androgen-insensitive LNCaPC4-2 and LNCaP-C81 cells compared to parental androgen-sensitive LNCaP cells. Ectopic expression of KIBRA enhances cell proliferation, migration and invasion in both immortalized and cancerous prostate epithelial cells...
May 2016: FEBS Journal
https://www.readbyqxmd.com/read/27123786/a-role-for-attention-during-wilderness-navigation-comparing-effects-of-bdnf-kibra-and-chrna4
#17
Ericka Rovira, Ryan S Mackie, Nicholas Clark, Peter N Squire, Michael D Hendricks, Alysse M Pulido, Pamela M Greenwood
OBJECTIVE: To better understand what influences interindividual differences in ability to navigate in the wilderness, we hypothesized that better performance would be seen in (a) BDNF (rs6265) Val/Val homozygotes increased use of a spatial strategy, (b) KIBRA rs17070145 T/T homozygotes superior episodic memory, (c) CHRNA4 (rs1044396) T allele carriers better ability to focus visuospatial attention. METHOD: Military cadets (n = 382) genotyped for BDNF, KIBRA, and CHRNA4 SNPs used a map and compass to navigate in unmarked woods...
September 2016: Neuropsychology
https://www.readbyqxmd.com/read/27100190/bad-ac-etylated-tau
#18
Jane C Hettinger, John R Cirrito
By using a tau construct with two mimicked acetylation sites as identified in AD brains, Tracy et al. (2016) found that acetylated tau promotes synaptic dysfunction through disruption of postsynaptic KIBRA signaling pathways, actin dynamics, and AMPA receptor trafficking.
April 20, 2016: Neuron
https://www.readbyqxmd.com/read/27041503/acetylated-tau-obstructs-kibra-mediated-signaling-in-synaptic-plasticity-and-promotes-tauopathy-related-memory-loss
#19
Tara E Tracy, Peter Dongmin Sohn, S Sakura Minami, Chao Wang, Sang-Won Min, Yaqiao Li, Yungui Zhou, David Le, Iris Lo, Ravikumar Ponnusamy, Xin Cong, Birgit Schilling, Lisa M Ellerby, Richard L Huganir, Li Gan
Tau toxicity has been implicated in the emergence of synaptic dysfunction in Alzheimer's disease (AD), but the mechanism by which tau alters synapse physiology and leads to cognitive decline is unclear. Here we report abnormal acetylation of K274 and K281 on tau, identified in AD brains, promotes memory loss and disrupts synaptic plasticity by reducing postsynaptic KIdney/BRAin (KIBRA) protein, a memory-associated protein. Transgenic mice expressing human tau with lysine-to-glutamine mutations to mimic K274 and K281 acetylation (tauKQ) exhibit AD-related memory deficits and impaired hippocampal long-term potentiation (LTP)...
April 20, 2016: Neuron
https://www.readbyqxmd.com/read/27015692/mecp2-impairs-neuronal-structure-by-regulating-kibra
#20
Alison A Williams, Robin White, Ashley Siniard, Jason Corneveaux, Matt Huentelman, Carsten Duch
Using a Drosophila model of MECP2 gain-of-function, we identified memory associated KIBRA as a target of MECP2 in regulating dendritic growth. We found that expression of human MECP2 increased kibra expression in Drosophila, and targeted RNAi knockdown of kibra in identified neurons fully rescued dendritic defects as induced by MECP2 gain-of-function. Validation in mouse confirmed that Kibra is similarly regulated by Mecp2 in a mammalian system. We found that Mecp2 gain-of-function in cultured mouse cortical neurons caused dendritic impairments and increased Kibra levels...
July 2016: Neurobiology of Disease
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