Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As constituents of lysosomes, lysosomal membrane proteins play important roles in lysosome-related autophagy and apoptosis. In a recent proteomic study of lysosomal proteins, we identified transmembrane protein 192 (TMEM192) as a novel lysosomal membrane protein candidate. Using specific anti-TMEM192 antibody and lysosomal markers, the lysosomal localization of TMEM192 was determined by immunofluorescence. TMEM192 shows a wide expression pattern in mouse tissues. Interestingly, TMEM192 was found to be highly expressed in tumor cell lines, while it was not expressed or was detected at low levels in normal cell lines. By knockdown of TMEM192 expression using specific siRNAs, we found that TMEM192-deficient HepG2 hepatoma cells show growth inhibition and increased apoptosis. Autophagy was shown to be activated through detection of LC3II expression. Increased apoptosis was inhibited by blocking the expression of the key autophagy gene Atg7 in TMEM192-deficient HepG2 cells. The results suggest that TMEM192 is important for tumor cell growth and proliferation. TMEM192 deficiency can induce autophagy in tumor cells, and can further activate apoptosis by the mitochondrial pathway through autophagy. TMEM192 promotion of autophagy may be a new route for tumor therapy.
 ...
PMID:Lysosomal membrane protein TMEM192 deficiency triggers crosstalk between autophagy and apoptosis in HepG2 hepatoma cells. 2273 46

The Transmembrane protein 192 (TMEM192) is a lysosomal/late endosomal protein initially discovered by organellar proteomics. TMEM192 exhibits four transmembrane segments with cytosolic N- and C-termini and forms homodimers. Devoid of significant homologies, the molecular function of TMEM192 is currently unknown. Upon TMEM192 knockdown in hepatoma cells, a dysregulation of autophagy and increased apoptosis were reported. Here, we aimed to define the physiological role of TMEM192 by analysing consequences of TMEM192 ablation in mice. Therefore, we compared the biochemical properties of murine TMEM192 to those of the human orthologue. We reveal lysosomal residence of murine TMEM192 and demonstrate ubiquitous tissue expression. In brain, TMEM192 expression was pronounced in the hippocampus but also present in the cortex and cerebellum, as analysed based on a lacZ reporter allele. Murine TMEM192 undergoes proteolytic processing in a tissue-specific manner. Thereby, a 17 kDa fragment is generated which was detected in most murine tissues except liver. TMEM192 processing occurs after lysosomal targeting by pH-dependent lysosomal proteases. TMEM192-/- murine embryonic fibroblasts (MEFs) exhibited a regular morphology of endo-/lysosomes and were capable of performing autophagy and lysosomal exocytosis. Histopathological, ultrastructural and biochemical analyses of all major tissues of TMEM192-/- mice demonstrated normal lysosomal functions without apparent lysosomal storage. Furthermore, the abundance of the major immune cells was comparable in TMEM192-/- and wild type mice. Based on this, we conclude that under basal conditions in vivo the loss of TMEM192 can be efficiently compensated by alternative pathways. Further studies will be required to decipher its molecular function.
 ...
PMID:Functional characterization of the lysosomal membrane protein TMEM192 in mice. 2850 66