Entrez Gene

General information | Expression | Regulation | Mutation | Interaction

Basic Information
Gene ID	9516
Name	LITAF
Synonymous	PIG7\|SIMPLE\|TP53I7;lipopolysaccharide-induced TNF factor;LITAF;lipopolysaccharide-induced TNF factor
Definition	LPS-induced TNF-alpha factor\|lipopolysaccharide-induced TNF-alpha factor\|lipopolysaccharide-induced tumor necrosis factor-alpha factor\|p53-induced gene 7 protein\|small integral membrane protein of lysosome/late endosome\|tumor protein p53 inducible protein
Position	16p13.13
Gene type	protein-coding
Source	Count: 1; Generif
Sentence	Abstract
studies for the first time establish the regulatory axis of AMPK-LITAF-TNFSF15 and also suggest that LITAF may function as a tumor suppressor	Lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) alpha factor (LITAF) is a multiple functional molecule whose sequence is identical to the small integral membrane protein of the lysosome/late endosome. LITAF was initially identified as a transcription factor that activates transcription of proinflammatory cytokine in macrophages in response to LPS. mutations of the LITAF gene are associated with a genetic disease, called Charcot-Marie-Tooth syndrome. Recently, we have reported that mRNA levels of LITAF and TNF superfamily member 15 (TNFSF15) are upregulated by 5' adenosine monophosphate (AMP)-activated protein kinase (AMPK). The present study further assesses their biological functions. Thus, we show that 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a pharmacological activator of AMPK, increases the abundance of LITAF and TNFSF15 in LNCaP and C4-2 prostate cancer cells, which is abrogated by small hairpin RNA (shRNA) or the dominant-negative mutant of AMPK alpha1 subunit. Our data further demonstrate that AMPK activation upregulates the transcription of LITAF. Intriguingly, silencing LITAF by shRNA enhances proliferation, anchorage-independent growth of these cancer cells and tumor growth in the xenograft model. In addition, our study reveals that LITAF mediates the effect of AMPK by binding to a specific sequence in the promoter region. Furthermore, we show that TNFSF15 remarkably inhibits the growth of prostate cancer cells and bovine aortic endothelial cells in vitro, with a more potent effect toward the latter. In conjuncture, intratumoral injection of TNFSF15 significantly reduces the size of tumors and number of blood vessels and induces changes that are characteristic of tumor cell differentiation. Therefore, our studies for the first time establish the regulatory axis of AMPK-LITAF-TNFSF15 and also suggest that LITAF may function as a tumor suppressor.