AP-57/C10orf99 is a new type of multifunctional antimicrobial peptide.

Antimicrobial peptides (AMPs) are an evolutionarily conserved component of the innate immune response that provides host defence at skin and mucosal surfaces. Here, we report the identification and characterization of a new type human AMPs, termed AP-57 (Antimicrobial Peptide with 57 amino acid residues), which is also known as C10orf99 (chromosome 10 open reading frame 99). AP-57 is a short basic amphiphilic peptide with four cysteines and a net charge +14 (MW = 6.52, PI = 11.28). The highest expression of AP-57 were detected in the mucosa of stomach and colon through immunohistochemical assay. Epithelium of skin and esophagus show obvious positive staining and strong positive staining were also observed in some tumor and/or their adjacent tissues, such as esophagus cancer, hepatocellular carcinoma, squamous cell carcinoma and invasive ductal carcinoma. AP-57 exhibited broad-spectrum antimicrobial activities against Gram-positive Staphylococcus aureus, Actinomyce, and Fungi Aspergillus niger as well as mycoplasma and lentivirus. AP-57 also exhibited DNA binding capacity and specific cytotoxic effects against human B-cell lymphoma Raji. Compared with other human AMPs, AP-57 has its distinct characteristics, including longer sequence length, four cysteines, highly cationic character, cell-specific toxicity, DNA binding and tissue-specific expressing patterns. Together, AP-57 is a new type of multifunctional AMPs worthy further investigation.

[1]  M. Zasloff Antimicrobial peptides of multicellular organisms , 2002, Nature.

[2]  Yuquan Wei,et al.  Increased expression of S100A6 promotes cell proliferation and migration in human hepatocellular carcinoma , 2013, Journal of Molecular Medicine.

[3]  M. Selsted,et al.  Mammalian defensins in the antimicrobial immune response , 2005, Nature Immunology.

[4]  Li Li,et al.  A mouse knockout library for secreted and transmembrane proteins , 2010, Nature Biotechnology.

[5]  I. Mellman,et al.  Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide , 2007, Nature.

[6]  R. Hancock,et al.  Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies , 2006, Nature Biotechnology.

[7]  Ying-wei Xie,et al.  Comparative Proteomic Approach Identifies Pkm2 and Cofilin-1 as Potential Diagnostic, Prognostic and Therapeutic Targets for Pulmonary Adenocarcinoma , 2011, PloS one.

[8]  J. Ji,et al.  CSBF/C10orf99, a novel potential cytokine, inhibits colon cancer cell growth through inducing G1 arrest , 2014, Scientific Reports.

[9]  Yuquan Wei,et al.  Proteomic profiling identifies aberrant epigenetic modifications induced by hepatitis B virus X protein. , 2009, Journal of proteome research.

[10]  D. Troyer,et al.  Phosphorylation of Akt (Ser473) is an Excellent Predictor of Poor Clinical Outcome in Prostate Cancer , 2004, Cancer Research.

[11]  M. Pazgier,et al.  Human α-Defensin 6 Promotes Mucosal Innate Immunity Through Self-Assembled Peptide Nanonets , 2012, Science.

[12]  Jerry Kaplan,et al.  Hepcidin Regulates Cellular Iron Efflux by Binding to Ferroportin and Inducing Its Internalization , 2004, Science.

[13]  Pui-Yan Kwok,et al.  Genomewide Scan Reveals Association of Psoriasis with IL-23 and NF-κB Pathways , 2008, Nature Genetics.

[14]  Zhu Yuan,et al.  HepG2.2.15 as a model for studying cell protrusion and migration regulated by S100 proteins. , 2014, Biochemical and biophysical research communications.

[15]  Guoqing Wang,et al.  Gene expression profile based classification models of psoriasis. , 2014, Genomics.

[16]  Jun Yuan,et al.  A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated alpha-defensins. , 1999, Science.

[17]  V. Nizet,et al.  Cutaneous defense mechanisms by antimicrobial peptides. , 2005, The Journal of investigative dermatology.