| 13432284 | LACTB is a filament-forming protein localized in mitochondria. | Polianskyte Z, etal., Proc Natl Acad Sci U S A. 2009 Nov 10;106(45):18960-5. doi: 10.1073/pnas.0906734106. Epub 2009 Oct 26. | LACTB is a mammalian active-site serine protein that has evolved from a bacterial penicillin-binding protein. Penicillin-binding proteins are involved in the metabolism of peptidoglycan, the major bacterial cell wall constituent, implying that LACTB weight:700;'>LACTB has been endowed with novel biochemical properties during eukaryote evolution. Here we demonstrate that LACTB is localized in the mitochondrial intermembrane space, where it is polymerized into stable filaments with a length extending more than a hundred nanometers. We infer that LACTB, through polymerization, promotes intramitochondrial membrane organization and micro-compartmentalization. These findings have implications for our understanding of mitochondrial evolution and function. | 19858488 | 2009-11-10 |
| 11096602 | MicroRNA-125b-5p attenuates lipopolysaccharide-induced monocyte chemoattractant protein-1 production by targeting inhibiting LACTB in THP-1 macrophages. | Lu JB, etal., Arch Biochem Biophys. 2016 Jan 15;590:64-71. doi: 10.1016/j.abb.2015.11.007. Epub 2015 Nov 18. | BACKGROUND: Increasing evidence has shown that gene beta-lactamases (LACTB) has effect on obesity. Recent studies demonstrate that miR-125b-5p is a potential small molecular target to prevent atherosclerosis obliterans which may be inflammation-associated. Howev er, the mechanism underlying miR-125b-5p on arteriosclerosis development, the association between miR-125b-5p and LACTB is still unknown. METHODS AND RESULTS: In this study, we found that miR-125b-5p was down-regulated while LACTB was up-regulated in atherosclerotic plaques. Our results showed that LACTB was a potential target of miR-125b-5p based on bioinformatics analyses and dual-luciferase reporter assays. Moreover, miR-125b-5p directly inhibited LACTB protein and mRNA expression by targeting LACTB 3'UTR. Meanwhile, the expression of monocyte chemotactic protein-1 (MCP-1) was decreased by miR-125b-5p mimics treatment in THP-1 macrophages. We also demonstrated that the level of MCP-1 was markedly increased when transfected with LACTB. In addition, the upregulation of MCP-1 expression through miR-125b-5p inhibitors was attenuate by siRNA-LACTB treatment in LPS-stimulated THP-1 macrophages. CONCLUSIONS: MiR-125b-5p attenuates the secretion of MCP-1 by directly targeting inhibiting LACTB in LPS-stimulated THP-1 macrophages. | 26603571 | 2016-06-01 |
| 11085507 | Disruption of NCOA2 by recurrent fusion with LACTB2 in colorectal cancer. | Yu J, etal., Oncogene. 2016 Jan 14;35(2):187-95. doi: 10.1038/onc.2015.72. Epub 2015 Mar 30. | Whole-genome and transcriptome sequencing were used to discover novel gene fusions in a case of colon cancer. A tumor-specific LACTB2-NCOA2 fusion originating from intra-chromosomal rearrangement of chromosome 8 was identified at both DNA and RNA levels. Unlike conventional oncogenic chimeric proteins, the fusion product lacks functional domain from respective genes, indicative of an amorphic rearrangement. This chimeric LACTB2-NCOA2 transcript was detected in 6 out of 99 (6.1%) colorectal cancer (CRC) cases, where NCOA2 was significantly downregulated. Enforced expression of wild-type NCOA2 but not the LACTB2-NCOA2 fusion protein impaired the pro-tumorigenic phenotypes of CRC cells, whereas knockdown of endogenous NCOA2 in normal colonocytes had opposite effects. Mechanistically, NCOA2 inhibited Wnt/beta-catenin signaling through simultaneously upregulating inhibitors and downregulating stimulators of Wnt/beta-catenin pathway. Collectively, our data supports that NCOA2 is a novel negative growth regulatory gene repressing the Wnt/beta-catenin pathway in CRC, where recurrent fusion with LACTB2 contributes to its disruption. | 25823027 | 2016-06-01 |
| 11352515 | Identification of LACTB2, a metallo-beta-lactamase protein, as a human mitochondrial endoribonuclease. | Levy S, etal., Nucleic Acids Res. 2016 Feb 29;44(4):1813-32. doi: 10.1093/nar/gkw050. Epub 2016 Jan 29. | Post-transcriptional control of mitochondrial gene expression, including the processing and generation of mature transcripts as well as their degradation, is a key regulatory step in gene expression in human mitochondria. Consequently, identification of the proteins responsible for RNA processing a nd degradation in this organelle is of great importance. The metallo-beta-lactamase (MBL) is a candidate protein family that includes ribo- and deoxyribonucleases. In this study, we discovered a function for LACTB2, an orphan MBL protein found in mammalian mitochondria. Solving its crystal structure revealed almost perfect alignment of the MBL domain with CPSF73, as well as to other ribonucleases of the MBL superfamily. Recombinant human LACTB2 displayed robust endoribonuclease activity on ssRNA with a preference for cleavage after purine-pyrimidine sequences. Mutational analysis identified an extended RNA-binding site. Knockdown of LACTB2 in cultured cells caused a moderate but significant accumulation of many mitochondrial transcripts, and its overexpression led to the opposite effect. Furthermore, manipulation of LACTB2 expression resulted in cellular morphological deformation and cell death. Together, this study discovered that LACTB2 is an endoribonuclease that is involved in the turnover of mitochondrial RNA, and is essential for mitochondrial function in human cells. | 26826708 | 2016-07-01 |
