LFG: a candidate apoptosis regulatory gene family

Abstract

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.

Lifeguard Inhibits Fas Ligand-mediated Endoplasmic Reticulum-Calcium Release Mandatory for Apoptosis in Type II Apoptotic Cells

“…LFG is highly homologous to BI-1 (15). BI-1 blocks the intrinsic pathway that protects cells from DNA-damaging agents and ER stress inducers (41,42).…”

“…DR activity can be modulated by a group of proteins called DR antagonists, such as FLIP (13), FAIM-L (Fas apoptotic inhibitory molecule) (14), and LFG. LFG is also known as FAIM2 or transmembrane Bax inhibitory motif (TMBIM) 2 (15). It was discovered in a screening for genes that conferred resistance to Fas-induced apoptosis (16).…”

Knockdown of the putative Lifeguard homologue CG3814 in neurons of Drosophila melanogaster

“…Lifeguard (LFG) or Fas apoptotic inhibitory molecule 2, also known as Transmembrane Bcl-2 associated protein X (Bax) inhibitor motif 2, belongs to a diverse membrane-spanning protein family (Hu et al, 2009;Rojas-Rivera and Hetz, 2015) and inhibits apoptosis mediated by the Fas/CD95/Apo-1 receptor but not the closely related TNFR (Somia et al, 1999). LFG was first identified as neuronal membrane protein 35 when it was found to be differentially upregulated during rat postnatal development (Schweitzer et al, 1998) and predominantly localized to the endoplasmic reticulum (ER).…”

“…LFG was first identified as neuronal membrane protein 35 when it was found to be differentially upregulated during rat postnatal development (Schweitzer et al, 1998) and predominantly localized to the endoplasmic reticulum (ER). A different nomenclature categorizes this protein into a family referred to as LFG, which is adopted from Lifeguard (Hu et al, 2009), and classifies LFG as LFG2. This conserved protein consists of seven transmembrane domains and is found in plants, insects, amphibians, fish, and mammals (Reimers et al, 2006).…”

Silencing of anti-apoptotic transmembrane protein lifeguard sensitizes solid tumor cell lines MCF-7 and SW872 to perifosine-induced cell death activation

“…Lifeguard (LFG), a member of a unique gene family with high structural similarity (1), was isolated and identified as a molecule that inhibits death mediated by Fas in tumor cells (2). The anti-apoptotic role of LFG was confirmed in LN-18 astrocytoma, and cervical carcinoma HeLa and Jurkat T cell lines (3).…”