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https://www.readbyqxmd.com/read/27821327/targeting-nitrative-stress-for-attenuating-cisplatin-induced-downregulation-of-cochlear-lim-domain-only-4-and-ototoxicity
#1
Samson Jamesdaniel, Rajamani Rathinam, William L Neumann
Cisplatin-induced ototoxicity remains a primary dose-limiting adverse effect of this highly effective anticancer drug. The clinical utility of cisplatin could be enhanced if the signaling pathways that regulate the toxic side-effects are delineated. In previous studies, we reported cisplatin-induced nitration of cochlear proteins and provided the first evidence for nitration and downregulation of cochlear LIM domain only 4 (LMO4) in cisplatin ototoxicity. Here, we extend these findings to define the critical role of nitrative stress in cisplatin-induced downregulation of LMO4 and its consequent ototoxic effects in UBOC1 cell cultures derived from sensory epithelial cells of the inner ear and in CBA/J mice...
December 2016: Redox Biology
https://www.readbyqxmd.com/read/27780223/lim-only-protein-4-lmo4-and-lim-domain-binding-protein-1-ldb1-promote-growth-and-metastasis-of-human-head-and-neck-cancer-lmo4-and-ldb1-in-head-and-neck-cancer
#2
Elizabeth A Simonik, Ying Cai, Katherine N Kimmelshue, Dana M Brantley-Sieders, Holli A Loomans, Claudia D Andl, Grant M Westlake, Victoria M Youngblood, Jin Chen, Wendell G Yarbrough, Brandee T Brown, Lalitha Nagarajan, Stephen J Brandt
Squamous cell carcinoma of the head and neck (HNSCC) accounts for more than 300,000 deaths worldwide per year as a consequence of tumor cell invasion of adjacent structures or metastasis. LIM-only protein 4 (LMO4) and LIM-domain binding protein 1 (LDB1), two directly interacting transcriptional adaptors that have important roles in normal epithelial cell differentiation, have been associated with increased metastasis, decreased differentiation, and shortened survival in carcinoma of the breast. Here, we implicate two LDB1-binding proteins, single-stranded binding protein 2 (SSBP2) and 3 (SSBP3), in controlling LMO4 and LDB1 protein abundance in HNSCC and in regulating specific tumor cell functions in this disease...
2016: PloS One
https://www.readbyqxmd.com/read/27354352/genome-wide-association-study-in-east-asians-identifies-two-novel-breast-cancer-susceptibility-loci
#3
Mi-Ryung Han, Jirong Long, Ji-Yeob Choi, Siew-Kee Low, Sun-Seog Kweon, Ying Zheng, Qiuyin Cai, Jiajun Shi, Xingyi Guo, Keitaro Matsuo, Motoki Iwasaki, Chen-Yang Shen, Mi Kyung Kim, Wanqing Wen, Bingshan Li, Atsushi Takahashi, Min-Ho Shin, Yong-Bing Xiang, Hidemi Ito, Yoshio Kasuga, Dong-Young Noh, Koichi Matsuda, Min Ho Park, Yu-Tang Gao, Hiroji Iwata, Shoichiro Tsugane, Sue K Park, Michiaki Kubo, Xiao-Ou Shu, Daehee Kang, Wei Zheng
Breast cancer is one of the most common malignancies among women worldwide. Genetic factors have been shown to play an important role in breast cancer etiology. We conducted a two-stage genome-wide association study (GWAS) including 14,224 cases and 14,829 controls of East Asian women to search for novel genetic susceptibility loci for breast cancer. Single nucleotide polymorphisms (SNPs) in two loci were found to be associated with breast cancer risk at the genome-wide significant level. The first locus, represented by rs12118297 at 1p22...
June 27, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/26814051/area-specific-development-of-distinct-projection-neuron-subclasses-is-regulated-by-postnatal-epigenetic-modifications
#4
Kawssar Harb, Elia Magrinelli, Céline S Nicolas, Nikita Lukianets, Laura Frangeul, Mariel Pietri, Tao Sun, Guillaume Sandoz, Franck Grammont, Denis Jabaudon, Michele Studer, Christian Alfano
During cortical development, the identity of major classes of long-distance projection neurons is established by the expression of molecular determinants, which become gradually restricted and mutually exclusive. However, the mechanisms by which projection neurons acquire their final properties during postnatal stages are still poorly understood. In this study, we show that the number of neurons co-expressing Ctip2 and Satb2, respectively involved in the early specification of subcerebral and callosal projection neurons, progressively increases after birth in the somatosensory cortex...
2016: ELife
https://www.readbyqxmd.com/read/26579872/lmo4-and-other-lim-domain-only-factors-are-necessary-and-sufficient-for-multiple-retinal-cell-type-development
#5
Kangxin Jin, Dongchang Xiao, Bogi Andersen, Mengqing Xiang
Understanding the molecular basis by which distinct cell types are specified is a central issue in retinogenesis and retinal disease development. Here we examined the role of LIM domain only 4 (Lmo4) in retinal development using both gain-of-function and loss-of-function approaches. By immunostaining, Lmo4 was found to be expressed in mouse retina from E10.5 to mature stages. Retroviral delivery of Lmo4 into retinal progenitor cells could promote the amacrine, bipolar and Müller cell fates at the expense of photoreceptors...
August 2016: Developmental Neurobiology
https://www.readbyqxmd.com/read/26292756/%C3%AF-secretase-and-larg-mediate-distinct-rgma-activities-to-control-appropriate-layer-targeting-within-the-optic-tectum
#6
P Banerjee, H Harada, N G Tassew, J Charish, D Goldschneider, V A Wallace, S Sugita, P Mehlen, P P Monnier
While a great deal of progress has been made in understanding the molecular mechanisms that regulate retino-tectal mapping, the determinants that target retinal projections to specific layers of the optic tectum remain elusive. Here we show that two independent RGMa-peptides, C- and N-RGMa, activate two distinct intracellular pathways to regulate axonal growth. C-RGMa utilizes a Leukemia-associated RhoGEF (LARG)/Rho/Rock pathway to inhibit axonal growth. N-RGMa on the other hand relies on ϒ-secretase cleavage of the intracellular portion of Neogenin to generate an intracellular domain (NeICD) that uses LIM-only protein 4 (LMO4) to block growth...
March 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/26134647/a-selective-role-for-lmo4-in-cue-reward-learning
#7
Rajani Maiya, Regina A Mangieri, Richard A Morrisett, Ulrike Heberlein, Robert O Messing
The ability to use environmental cues to predict rewarding events is essential to survival. The basolateral amygdala (BLA) plays a central role in such forms of associative learning. Aberrant cue-reward learning is thought to underlie many psychopathologies, including addiction, so understanding the underlying molecular mechanisms can inform strategies for intervention. The transcriptional regulator LIM-only 4 (LMO4) is highly expressed in pyramidal neurons of the BLA, where it plays an important role in fear learning...
July 1, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/26048572/the-lim-domain-only-protein-4-contributes-to-lung-epithelial-cell-proliferation-but-is-not-essential-for-tumor-progression
#8
Aliaksei Z Holik, Caitlin E Filby, Julie Pasquet, Kati Viitaniemi, John Ciciulla, Kate D Sutherland, Marie-Liesse Asselin-Labat
BACKGROUND: The lung is constantly exposed to environmental challenges and must rapidly respond to external insults. Mechanisms involved in the repair of the damaged lung involve expansion of different epithelial cells to repopulate the injured cellular compartment. However, factors regulating cell proliferation following lung injury remain poorly understood. Here we studied the role of the transcriptional regulator Lmo4 during lung development, in the regulation of adult lung epithelial cell proliferation following lung damage and in the context of oncogenic transformation...
June 7, 2015: Respiratory Research
https://www.readbyqxmd.com/read/25994864/gwa-meta-analysis-of-personality-in-korean-cohorts
#9
Bo-Hye Kim, Han-Na Kim, Seung-Ju Roh, Mi Kyeong Lee, Sarah Yang, Seung Ku Lee, Yeon-Ah Sung, Hye Won Chung, Nam H Cho, Chol Shin, Joohon Sung, Hyung-Lae Kim
Personality is a determinant of behavior and lifestyle that is associated with health and human diseases. Despite the heritability of personality traits is well established, the understanding of the genetic contribution to personality trait variation is extremely limited. To identify genetic variants associated with each of the five dimensions of personality, we performed a genome-wide association (GWA) meta-analysis of three cohorts, followed by comparison of a family cohort. Personality traits were measured with the Revised NEO Personality Inventory for the five-factor model (FFM) of personality...
August 2015: Journal of Human Genetics
https://www.readbyqxmd.com/read/25991585/microrna-409-3p-suppresses-colorectal-cancer-invasion-and-metastasis-partly-by-targeting-gab1-expression
#10
Rongpan Bai, Chunhua Weng, Haojie Dong, Siqi Li, Guangdi Chen, Zhengping Xu
Colorectal cancer (CRC) is one of the most common cancers worldwide and its metastasis accounts for the majority of deaths. However, the molecular mechanisms underlying CRC progression are not well characterized. In this study, we identified miR-409-3p as a tumor suppressor of CRC. MiR-409-3p expression was significantly downregulated in CRC tissue compared to adjacent non-tumor tissue, and reduced miR-409-3p expression was correlated with CRC metastasis. In vitro and in vivo studies revealed that miR-409-3p negatively regulated CRC metastatic capacities, including suppressing cancer cell migration, invasion and metastasis...
November 15, 2015: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/25941476/molecular-codes-defining-rostrocaudal-domains-in-the-embryonic-mouse-hypothalamus
#11
José L Ferran, Luis Puelles, John L R Rubenstein
The prosomeric model proposes that the hypothalamus is a rostral forebrain entity, placed ventral to the telencephalon and rostral to the diencephalon. Gene expression markers differentially label molecularly distinct dorsoventral progenitor domains, which represent continuous longitudinal bands across the hypothalamic alar and basal regions. There is also circumstantial support for a rostrocaudal subdivision of the hypothalamus into transverse peduncular (caudal) and terminal (rostral) territories (PHy, THy)...
2015: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/25882817/recruitment-and-activation-of-slk-at-the-leading-edge-of-migrating-cells-requires-src-family-kinase-activity-and-the-lim-only-protein-4
#12
Kyla D Baron, Khalid Al-Zahrani, Jillian Conway, Cédrik Labrèche, Christopher J Storbeck, Jane E Visvader, Luc A Sabourin
The Ste20-like kinase SLK plays a pivotal role in cell migration and focal adhesion turnover and is regulated by the LIM domain-binding proteins Ldb1 and Ldb2. These adapter proteins have been demonstrated to interact with LMO4 in the organization of transcriptional complexes. Therefore, we have assessed the ability of LMO4 to also interact and regulate SLK activity. Our data show that LMO4 can directly bind to SLK and activate its kinase activity in vitro and in vivo. LMO4 can be co-precipitated with SLK following the induction of cell migration by scratch wounding and Cre-mediated deletion of LMO4 in conditional LMO4(fl/fl) fibroblasts inhibits cell migration and SLK activation...
July 2015: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/25754825/chronic-stress-induces-anxiety-via-an-amygdalar-intracellular-cascade-that-impairs-endocannabinoid-signaling
#13
Zhaohong Qin, Xun Zhou, Nihar R Pandey, Haley A Vecchiarelli, Chloe A Stewart, Xia Zhang, Diane C Lagace, Jean Michel Brunel, Jean-Claude Béïque, Alexandre F R Stewart, Matthew N Hill, Hsiao-Huei Chen
Collapse of endocannabinoid (eCB) signaling in the amygdala contributes to stress-induced anxiety, but the mechanisms of this effect remain unclear. eCB production is tied to the function of the glutamate receptor mGluR5, itself dependent on tyrosine phosphorylation. Herein, we identify a novel pathway linking eCB regulation of anxiety through phosphorylation of mGluR5. Mice lacking LMO4, an endogenous inhibitor of the tyrosine phosphatase PTP1B, display reduced mGluR5 phosphorylation, eCB signaling, and profound anxiety that is reversed by genetic or pharmacological suppression of amygdalar PTP1B...
March 18, 2015: Neuron
https://www.readbyqxmd.com/read/25698932/opportunities-and-limits-of-the-one-gene-approach-the-ability-of-atoh1-to-differentiate-and-maintain-hair-cells-depends-on-the-molecular-context
#14
REVIEW
Israt Jahan, Ning Pan, Bernd Fritzsch
Atoh1 (Math1) was the first gene discovered in ear development that showed no hair cell (HC) differentiation when absent and could induce HC differentiation when misexpressed. These data implied that Atoh1 was both necessary and sufficient for hair cell development. However, other gene mutations also result in loss of initially forming HCs, notably null mutants for Pou4f3, Barhl1, and Gfi1. HC development and maintenance also depend on the expression of other genes (Sox2, Eya1, Gata3, Pax2) and several genes have been identified that can induce HCs when misexpressed (Jag1) or knocked out (Lmo4)...
2015: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/25613065/preliminary-screening-of-differentially-expressed-genes-involved-in-methyl-cpg-binding-protein-2-gene-mediated-proliferation-in-human-osteosarcoma-cells
#15
Gang Meng, Yi Li, YangFan Lv, Huanzi Dai, Xi Zhang, Qiao-Nan Guo
Methyl-CpG-binding protein 2 (MeCP2) is essential in human brain development and has been linked to several cancer types and neuro-developmental disorders. This study aims to screen the MeCP2 related differentially expressed genes and discover the therapeutic targets for osteosarcoma. CCK8 assay was used to detect the proliferation and SaOS2 and U2OS cells. Apoptosis of cells was detected by flow cytometry analysis that monitored Annexin V-APC/7-DD binding and 7-ADD uptake simultaneously. Denaturing formaldehyde agarose gel electrophoresis was employed to examine the quality of total RNA 18S and 28S units...
April 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/25501662/downstream-targets-of-lmo4-are-modulated-by-cisplatin-in-the-inner-ear-of-wistar-rats
#16
Samson Jamesdaniel
Lmo4, a transcriptional regulator, appears to be a key player in mediating the cochlear pathology in cisplatin ototoxicity, as it controls cellular responses by modulating the formation of transcriptional complexes. We provided the first evidence of in vivo nitration of Lmo4 in cisplatin ototoxicity. Our data suggested that nitration of Lmo4 and associated decrease in its cochlear expression has the potential to play a pivotal role in cisplatin ototoxicity. However, the Lmo4 interactomes that signal the downstream events in the cochlea are poorly understood...
2014: PloS One
https://www.readbyqxmd.com/read/25310299/the-structure-of-an-lim-only-protein-4-lmo4-and-deformed-epidermal-autoregulatory-factor-1-deaf1-complex-reveals-a-common-mode-of-binding-to-lmo4
#17
Soumya Joseph, Ann H Kwan, Philippa H Stokes, Joel P Mackay, Liza Cubeddu, Jacqueline M Matthews
LIM-domain only protein 4 (LMO4) is a widely expressed protein with important roles in embryonic development and breast cancer. It has been reported to bind many partners, including the transcription factor Deformed epidermal autoregulatory factor-1 (DEAF1), with which LMO4 shares many biological parallels. We used yeast two-hybrid assays to show that DEAF1 binds both LIM domains of LMO4 and that DEAF1 binds the same face on LMO4 as two other LMO4-binding partners, namely LIM domain binding protein 1 (LDB1) and C-terminal binding protein interacting protein (CtIP/RBBP8)...
2014: PloS One
https://www.readbyqxmd.com/read/25110573/seizure-evoked-regulation-of-lim-hd-genes-and-co-factors-in-the-postnatal-and-adult-hippocampus
#18
Vanisha Lakhina, Lakshmi Subramanian, Dhananjay Huilgol, Ashwin S Shetty, Vidita A Vaidya, Shubha Tole
The LIM-homeodomain (LIM-HD) family of transcription factors is well known for its functions during several developmental processes including cell fate specification, cell migration and axon guidance, and its members play fundamental roles in hippocampal development. The hippocampus is a structure that displays striking activity dependent plasticity.  We examined whether LIM-HD genes and their co-factors are regulated during kainic acid induced seizure in the adult rat hippocampus as well as in early postnatal rats, when the hippocampal circuitry is not fully developed...
2013: F1000Research
https://www.readbyqxmd.com/read/25079073/the-co-factor-of-lim-domains-clim-ldb-nli-maintains-basal-mammary-epithelial-stem-cells-and-promotes-breast-tumorigenesis
#19
Michael L Salmans, Zhengquan Yu, Kazuhide Watanabe, Eric Cam, Peng Sun, Padhraic Smyth, Xing Dai, Bogi Andersen
Mammary gland branching morphogenesis and ductal homeostasis relies on mammary stem cell function for the maintenance of basal and luminal cell compartments. The mechanisms of transcriptional regulation of the basal cell compartment are currently unknown. We explored these mechanisms in the basal cell compartment and identified the Co-factor of LIM domains (CLIM/LDB/NLI) as a transcriptional regulator that maintains these cells. Clims act within the basal cell compartment to promote branching morphogenesis by maintaining the number and proliferative potential of basal mammary epithelial stem cells...
July 2014: PLoS Genetics
https://www.readbyqxmd.com/read/25071464/combinatorial-expression-of-lef1-lhx2-lhx5-lhx9-lmo3-lmo4-and-prox1-helps-to-identify-comparable-subdivisions-in-the-developing-hippocampal-formation-of-mouse-and-chicken
#20
Antonio Abellán, Ester Desfilis, Loreta Medina
We carried out a study of the expression patterns of seven developmental regulatory genes (Lef1, Lhx2, Lhx9, Lhx5, Lmo3, Lmo4, and Prox1), in combination with topological position, to identify the medial pallial derivatives, define its major subdivisions, and compare them between mouse and chicken. In both species, the medial pallium is defined as a pallial sector adjacent to the cortical hem and roof plate/choroid tela, showing moderate to strong ventricular zone expression of Lef1, Lhx2, and Lhx9, but not Lhx5...
2014: Frontiers in Neuroanatomy
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