Serine beta-lactamase-like protein LACTB, mitochondrial is an enzyme that in humans is encoded by the LACTBgene.[1][2] This gene encodes a 54 kDa protein sharing significant
sequence similarity to serine proteases of the penicillin binding protein and beta-lactamase superfamily occurring in bacteria.
[3] It is involved in the regulation of the metabolic circuitry. A causal association has been found between LACTB and obesity. [4] In breast cancer, LACTB has a tumor suppressor function by modulating lipid metabolism.[5]
LACTB shares sequence similarity to the beta-lactamase/penicillin-binding protein family of serineproteases that are involved in bacterial cell wall metabolism. The N-terminal 97 amino acid segment of LACTB does not form part of the conserved penicillin-binding protein domain and may therefore be responsible for organelle targeting.[3][6]
Function
LACTB is widely expressed in different mammalian tissues, with the predominant expression in human skeletal muscle. It localizes in the mitochondrial intermembrane space.[6] LACTB can polymerize into stable filaments occupying the mitochondrial intermembrane space. These filaments are speculated to play a role in submitochondrial organization and therefore possibly affect mitochondrial metabolon organization. [6]
Clinical significance
It has been found LACTB could cause obesity through gene co-expression analysis based on data integrated from multiple sources. This has been validated in vivo through LACTB overexpression in transgenic mice, which resulted in an obese phenotype.[4] LACTB has also been identified to be a tumor suppressor through its effect on mitochondrial phospholipid metabolism and modulation of cell differentiation state.[7]
↑Keckesova et al. 2017. LACTB is a tumour supresssor that modulates lipid metabolism and cell state. Nature 543:681-686
↑Lu JB, Yao XX, Xiu JC, Hu YW (January 2016). "MicroRNA-125b-5p attenuates lipopolysaccharide-induced monocyte chemoattractant protein-1 production by targeting inhibiting LACTB in THP-1 macrophages". Archives of Biochemistry and Biophysics. 590: 64–71. doi:10.1016/j.abb.2015.11.007. PMID26603571.
Further reading
Hallis TM, Kopp AL, Gibson J, Lebakken CS, Hancock M, Van Den Heuvel-Kramer K, Turek-Etienne T (August 2007). "An improved beta-lactamase reporter assay: multiplexing with a cytotoxicity readout for enhanced accuracy of hit identification". Journal of Biomolecular Screening. 12 (5): 635–44. doi:10.1177/1087057107301499. PMID17517902.
Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID17081983.
Hell-Pourmojib M, Neuner P, Fischer H, Rezaie S, Kindås-Mügge I, Knobler R, Trautinger F (July 2002). "Differential expression of a novel gene in response to hsp27 and cell differentiation in human keratinocytes". The Journal of Investigative Dermatology. 119 (1): 154–9. doi:10.1046/j.1523-1747.2002.01793.x. PMID12164938.
Koc EC, Burkhart W, Blackburn K, Moyer MB, Schlatzer DM, Moseley A, Spremulli LL (November 2001). "The large subunit of the mammalian mitochondrial ribosome. Analysis of the complement of ribosomal proteins present". The Journal of Biological Chemistry. 276 (47): 43958–69. doi:10.1074/jbc.M106510200. PMID11551941.
