Comparative genomics and function analysis on BI1 family

Zhou, Jinhua; Zhu, Tao; Hu, Chunxia; Li, Hongyu; Chen, Gang; Xu, Gang; Wang, Shixuan; Zhou, Jianfeng; Ma, Ding

doi:10.1016/j.compbiolchem.2008.01.002

Cited by 19 publications

(18 citation statements)

References 23 publications

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“…GRINA, initially identified as a 71 kDa glutamate binding subunit (GBP) (Chen et al, 1988, Eaton et al, 1990, Kumar et al, 1991, Ly and Michaelis, 1991) is a member of a protein family characterized by the presence of conserved BAX inhibitor-1 (BI1) motifs (Zhou et al, 2008) embedded in seven transmembrane scaffold (Hu et al, 2009). GRINA is localized to neuronal cell bodies (Pal et al, 1999) and dendrites in the brain and spinal cord (Eaton et al, 1990).…”

Section: Discussionmentioning

confidence: 99%

Gene expression analysis of novel genes in the prefrontal cortex of major depressive disorder subjects

Goswami

Jernigan

Chandran

et al. 2013

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Dysregulation of the glutamatergic system has been implicated not only in the treatment of major depressive disorder (MDD), but also in the excitotoxic effects of stress and anxiety on the prefrontal cortex, which may precede the onset of a depressive episode. Our previous studies demonstrate marked deficits in prominent postsynaptic proteins involved in glutamate neurotransmission in the prefrontal cortex (PFC), Brodmann’s area 10 (BA 10) from subjects diagnosed with major depressive disorder (MDD). In the same group of subjects we have identified deficits in expression and phosphorylation level of key components of the mammalian target of rapamycin (mTOR) signalling pathway, known to regulate translation initiation. Based on our previous findings, we have postulated that glutamate-dependent dysregulation of mTOR- initiated protein synthesis in the PFC may underlie the pathology of MDD. The aim of this study was to use the NanoString nCounter System to perform analysis of genes coding for glutamate transporters, glutamate metabolizing enzymes, neurotrophic factors and other intracellular signaling markers involved in glutamate signaling that were not previously investigated by our group in the PFC BA10 from subjects with MDD. We have analyzed a total of 200 genes from 16 subjects with MDD and 16 healthy controls. These are part of the same cohort used in our previous studies. Setting our cutoff p-value ≤ 0.01, marked upregulation of genes coding for mitochondrial glutamate carrier (GC1; p=0.0015), neuropilin 1 (NRP-1; p=0.0019), glutamate receptor ionotropic N-methyl-D-aspartate-associated protein 1 (GRINA; p=0.0060), and fibroblast growth factor receptor 1 (FGFR-1; p=0.010) was identified. No significant differences in expression of the remaining 196 genes were observed between MDD subjects and controls. While upregulation of FGFR-1 has been previously shown in MDD; abnormalities in GC-1, GRINA, and NRP-1 have not been reported. Therefore, this postmortem study identifies GC1, GRINA, and NRP-1 as novel factors associated with MDD; however, future studies will be needed to address the significance of these genes in the pathophysiology of depression and antidepressant activity.

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Section: Discussionmentioning

confidence: 99%

Gene expression analysis of novel genes in the prefrontal cortex of major depressive disorder subjects

Goswami

Jernigan

Chandran

et al. 2013

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…Despite its role in altering TGF-beta signaling, association of this gene with cancer or its alteration in tumorigenesis has not been previously reported. TMBIM4 (or GAAP) is a novel anti-apoptotic regulator that belongs to a family of Bax-inhibitor-1 proteins that can bind to Bcl-2 family members and regulate cell death(39). TMBIM4 is ubiquitously expressed in all tissues, including the lungs.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Study of Genetic Predictors of Overall Survival for Non–Small Cell Lung Cancer in Never Smokers

Wang

et al. 2013

Cancer Research

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To identify the genetic factors that influence overall survival in never smokers who have non-small cell lung cancer (NSCLC), we performed a consistency meta-analysis study utilizing genome-wide association approaches for overall survival in 327 never smoker NSCLC patients from the MD Anderson Cancer Center and 293 cases from the Mayo Clinic. We then performed a two-pronged validation of the top 25 variants that included additional validation in 1,256 NSCLC patients from Taiwan and assessment of expression quantitative trait loci (eQTL) and differential expression of genes surrounding the top loci in 70 tumors and matched normal tissues. A total of 94 loci were significant for overall survival in both MD Anderson and Mayo studies in the consistency meta-analysis phase, with the top 25 variants reaching a p-value of 10−6. Two variants of these 25 were also significant in the Taiwanese population: rs6901416 (HR:1.44, 95%CI:1.01-2.06) and rs10766739 (HR:1.23, 95%CI:1.00-1.51). These loci resulted in a reduction in median survival time of at least 8 and 5 months in three populations, respectively. An additional six variants (rs4237904, rs7976914, rs4970833, rs954785, rs485411, and rs10906104) were validated through eQTL analysis that identified significant correlations with expression levels of six genes (LEMD3, TMBIM, ATXN7L2, SHE, ITIH2, and NUDT5, respectively) in normal lung tissue. These genes were also significantly differentially expressed between the tumor and normal lung. These findings identify several novel, candidate prognostic markers for NSCLC in never smokers, with eQTL analysis suggesting a potential biological mechanism for a subset of these observed associations.

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“…The transmembrane Bax inhibitor 1 (BI1) motif containing family has been reported to consist of at least seven mammalian proteins/genes, GRINA, BI1, Lfg/FAIM2, Ghitm, RESC1/Tmbim1, GAAP/Tmbim4, and Tmbm1b [1,2]. Three, BI1, Lfg, and GAAP, have been reported to play a modulatory role in apoptosis.…”

Section: Introductionmentioning

confidence: 99%

LFG: a candidate apoptosis regulatory gene family

2009

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The expanding wealth of human, model and other organism's genomic data has allowed the identification of a distinct gene family of apoptotic related genes. Most of these genes are currently unannotated or have been subsumed under two questionably related gene families in the past. For example the transmembrane Bax inhibitor 1 (BI1) motif family has been reported to play a role in apoptosis and to consist of at least seven mammalian protein genes, GRINA, BI1, Lfg/FAIM2, Ghitm, RESC1/Tmbim1, GAAP/Tmbim4, and Tmbm1b. However, a detailed sequence and phylogenetic analysis shows that only five of these form a clear and unique protein family. This now provides information for understanding and investigating the biological roles of these proteins across a wide range of tissues in model organisms. The evolutionary relationships among these genes provide a powerful prospective for extrapolating to human conditions.

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Comparative genomics and function analysis on BI1 family

Cited by 19 publications

References 23 publications

Gene expression analysis of novel genes in the prefrontal cortex of major depressive disorder subjects

Gene expression analysis of novel genes in the prefrontal cortex of major depressive disorder subjects

Genome-Wide Association Study of Genetic Predictors of Overall Survival for Non–Small Cell Lung Cancer in Never Smokers

LFG: a candidate apoptosis regulatory gene family

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