Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The full-length cDNA clone of a novel GRP78-binding protein (GBP) was isolated from rat brain using PCR-selected cDNA subtraction. GBP was predominantly expressed in neuronal cells among various brain tissues. GBP mRNA was already detected in the E12 brain and then gradually increased to reach a peak within P0-2 weeks after birth. GBP expression in the brain decreased age-dependently to approximately 30% of the postnatal level at 12 months. GBP encoded 1021 amino acids and was predicted to have two transmembrane regions and glutamic acid- and proline-rich regions. Because the sequence of GBP offered few clues to the possible function, we performed a GST-tagged GBP pull-down assay in PC12 lysates and identified GRP78, one of the heat shock proteins, as a counterpart. Observation of COS7 cells expressing green fluorescent protein- or Myc-tagged GBP showed that GBP was localized in the endoplasmic reticulum-Golgi domain where BODIPY 558/568 (4,4-difluro-5-(2-thienyl)-4-bora-3alpha,4alpha-diaza-S-indacene)-labeled brefeldin A accumulated. To investigate a biological role for GBP, we established Neuro2a cells stably expressing Myc-tagged GBP. Overexpression of GBP did not affect cell growth or morphological features but attenuated the time-dependent decrease in cell viability caused by serum deprivation compared with control cells. After 48 h of serum starvation, Neuro2a cells overexpressing GBP were resistant to the cell death induced by serum withdrawal. These results suggest that GBP would have a relevant functional role in embryonic and postnatal development of the brain.
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PMID:Cloning and characterization of a novel GRP78-binding protein in the rat brain. 1251 90

Transmembrane protein 132A (TMEM132A) is a novel GRP78 binding protein that we recently discovered. However, the biological functions of TMEM132A are merely characterized because it does not encode any known structural domains. In this study, we down regulated intrinsic TMEM132A by RNA interference and identified a variety of genes that fluctuated during TMEM132A gene silencing using microarray analysis. TMEM132A-knockdown in Neuro2a cells caused neurite-like projection without any stimuli and enhanced the expression of ATF6 mRNA, an ER stress transducer, and GADD153 mRNA, a stress inducible gene. Under serum-deprived condition, TMEM132A-knockdown cells gradually retarded neurite-like projection and decreased cell viability. Moreover, TMEM132A knockdown markedly induced GADD153 expression due to serum starvation without affecting the level of cleaved caspase-3. Our data suggest that TMEM132A is an important factor of cell survival in regulating certain ER stress-related gene expression in neuronal cells.
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PMID:Knockdown of transmembrane protein 132A by RNA interference facilitates serum starvation-induced cell death in Neuro2a cells. 2045 9

Transmembrane protein 132A (TMEM132A) was first isolated from rat brain using PCR-selected cDNA subtraction, and it was found to be predominantly expressed in the brain. However, the transcriptional regulation of the TMEM132A gene has not been fully characterized. In this study, we characterized the promoter activity of the 880-bp region upstream of the mouse TMEM132A, identifying several putative sites recognized by transcription factors, which are highly conserved between the mouse and human TMEM132A genes. Using four different mouse cell lines (Neuro2a, NSC-34, NIH3T3, and Raw264.7), we first evaluated the intrinsic levels of TMEM132A mRNA and protein expression. Interestingly, TMEM132A mRNA was expressed in all four cell lines, whereas the protein was negligible in Raw264.7 cells even by transfection of TMEM132A gene. Then, we analyzed the TMEM132A promoter activity using serial deleted constructs, finding it was nearly same pattern in all four cell lines. A mutational analysis of the TMEM132A promoter identified a critical region for its activation just upstream of the transcriptional start site. Finally, we investigated the levels of TMEM132A mRNA and protein after exposure to five different neurotoxic stimuli, including thapsigargin, tunicamycin, serum starvation, homocysteine, and hydrogen peroxide. Treatment with thapsigargin, a calcium modulating agent, markedly attenuated the levels of TMEM132A mRNA and protein in NSC-34 cells. These results give new insight into the mechanisms involved in regulating TMEM132A expression, and suggest that several transcriptional and post-transcriptional pathways regulate TMEM132A expression under developmental and pathophysiological conditions.
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PMID:Transcriptional and post-transcriptional regulation of transmembrane protein 132A. 2592 56