ARL14 is a 196-amino-acid GTPase encoded by the ARL14 gene located on chromosome 13q14.2 . As a member of the ARL subfamily, it regulates membrane trafficking and cytoskeletal dynamics through GTP-dependent interactions with effector proteins. Key functional partners include:
ARL14 also interacts with ESCPE-1 complex components (e.g., SNX1) to regulate retrograde cargo trafficking .
Vesicle Transport: ARL14 recruits MYO1E to MHC II-containing vesicles via ARL14EP, enabling actin-dependent movement in dendritic cells .
Cytoskeletal Regulation: Activates CDC42BPA/CDC42BPB and MYO18A to phosphorylate myosin light chain (MYL9/MLC2), promoting actomyosin assembly and cell migration .
Inflammatory Signaling: Indirectly activates NF-κB pathways via LURAP1, enhancing proinflammatory cytokine production .
In NSCLC, ARL14 overexpression correlates with:
CIDEC/ERK/p38 Pathway: Silencing ARL14 inhibits CIDEC-mediated ERK/p38 signaling, reducing tumor cell invasion .
Immune Cell Infiltration: ssGSEA analysis reveals associations with neutrophil degranulation and interleukin signaling in squamous carcinomas .
High ARL14 Expression: Enriched in keratinization (adenocarcinoma) and HDAC-mediated histone deacetylation .
Prognostic Biomarker: Nomograms integrating ARL14 expression with clinical variables (age, N stage) predict 1-, 3-, and 5-year survival .
Therapeutic Target: Silencing ARL14 in lung adenocarcinoma cells suppresses growth and metastasis, with minimal effects on normal cells .
Tissue-Specific Expression: Recent BioID data suggest ARL14 is restricted to stomach/intestines, but its role in gastrointestinal cancers remains unexplored .
PLD1 Activation: ARL14’s ability to activate PLD1 in cellulo warrants further study to elucidate lipid signaling mechanisms .
Immune Modulation: Links to NF-κB and cytokine production necessitate investigation into ARL14’s role in tumor microenvironment regulation .
ADP-ribosylation factor-like protein 14, ADP-ribosylation factor 7, ARL14, ARF7, FLJ22595.
MGSSHHHHHH SSGLVPRGSH MGSLGSKNPQ TKQAQVLLLG LDSAGKSTLL YKLKLAKDIT TIPTIGFNVE MIELERNLSL TVWDVGGQEK MRTVWGCYCE NTDGLVYVVD STDKQRLEES QRQFEHILKN EHIKNVPVVL LANKQDMPGA LTAEDITRMF KVKKLCSDRN WYVQPCCALT GEGLAQGFRK LTGFVKSHMK SRGDTLAFFK QN.
The ARL14 gene is located on chromosome 3 and encodes a protein that is 192 amino acids in length . The protein is expressed in various tissues and is involved in the regulation of vesicle movement along the actin cytoskeleton in dendritic cells . This movement is facilitated by the recruitment of MYO1E to MHC class II-containing vesicles via the effector protein ARL14EP .
ARL14 plays a crucial role in the immune system by controlling the movement of MHC class II-containing vesicles, which are essential for antigen presentation in dendritic cells . This function is vital for the immune response, as it helps in the activation of T-cells by presenting antigens on the cell surface .
Recombinant human ARL14 protein is produced using Escherichia coli expression systems and is purified to a high degree of purity (>90%) . This recombinant protein is used in various research applications, including mass spectrometry (MS) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) . The recombinant protein retains the functional properties of the native protein, making it a valuable tool for studying the biological functions of ARL14 .
Recent studies have suggested that ARL14 may serve as a prognostic biomarker in non-small cell lung cancer (NSCLC) . The expression levels of ARL14 have been correlated with the progression of NSCLC, indicating its potential role in cancer biology . Further research is needed to fully understand the implications of ARL14 in cancer and other diseases.