Finding one's way in proteomics: a protein species nomenclature

Our knowledge of proteins has greatly improved in recent years, driven by new technologies in the fields of molecular biology and proteome research. It has become clear that from a single gene not only one single gene product but many different ones - termed protein species - are generated, all of which may be associated with different functions. Nonetheless, an unambiguous nomenclature for describing individual protein species is still lacking. With the present paper we therefore propose a systematic nomenclature for the comprehensive description of protein species. The protein species nomenclature is flexible and adaptable to every level of knowledge and of experimental data in accordance with the exact chemical composition of individual protein species. As a minimum description the entry name (gene name + species according to the UniProt knowledgebase) can be used, if no analytical data about the target protein species are available

ScFv Anti-Heparan Sulfate Antibodies Unexpectedly Activate Endothelial and Cancer Cells through p38 MAPK: Implications for Antibody-Based Targeting of Heparan Sulfate Proteoglycans in Cancer

Contains fulltext : 109451.pdf (publisher's version ) (Open Access)Tumor development requires angiogenesis and anti-angiogenic therapies have been introduced in the treatment of cancer. In this context, heparan sulfate proteoglycans (HSPGs) emerge as interesting targets, owing to their function as co-receptors of major, pro-angiogenic factors. Accordingly, previous studies have suggested anti-tumor effects of heparin, i.e. over-sulfated HS, and various heparin mimetics; however, a significant drawback is their unspecific mechanism of action and potentially serious side-effects related to their anticoagulant properties. Here, we have explored the use of human ScFv anti-HS antibodies (alphaHS) as a more rational approach to target HSPG function in endothelial cells (ECs). alphaHS were initially selected for their recognition of HS epitopes localized preferentially to the vasculature of patient glioblastoma tumors, i.e. highly angiogenic brain tumors. Unexpectedly, we found that these alphaHS exhibited potent pro-angiogenic effects in primary human ECs. alphaHS were shown to stimulate EC differentiation, which was associated with increased EC tube formation and proliferation. Moreover, alphaHS supported EC survival under hypoxia and starvation, i.e. conditions typical of the tumor microenvironment. Importantly, alphaHS-mediated proliferation was efficiently counter-acted by heparin and was absent in HSPG-deficient mutant cells, confirming HS-specific effects. On a mechanistic level, binding of alphaHS to HSPGs of ECs as well as glioblastoma cells was found to trigger p38 MAPK-dependent signaling resulting in increased proliferation. We conclude that several alphaHS that recognize HS epitopes abundant in the tumor vasculature may elicit a pro-angiogenic response, which has implications for the development of antibody-based targeting of HSPGs in cancer