An extracellular proteasome releases endostatin from human collagen XVIII

Autor(es)

Reiss-Pistilli, Maria L. V. ; Schuppan, Detlef ; Barroso, Madalena M. S. ; Assuncao-Miranda, Iranaia ; Farias, Shirley ; Lery, Leticia ; Bauer, Michael ; Juliano, Luiz ; Juliano, Maria A. ; Coelho-Sampaio, Tatiana

• Tipo de documento: Artigo Científico
• Fonte: ANGIOGENESIS; v. 20, n. 1, p. 125-137, FEB 2017.
• Citações Web of Science: 1

Resumo

Endostatin is a potent anti-angiogenic and anti-tumor protein capable of regressing tumors without inducing acquired resistance. Since it is a fragment of the parental molecule, collagen XVIII, its endogenous production depends on the activity of a specific proteolytic enzyme. While such an enzyme has been described in mice, a human counterpart has not been identified so far. Here, we searched for this enzyme by using a fluorescence resonance energy transfer peptide containing the cleavage site of human collagen XVIII. We found that the cleavage activity was present in various murine and human tumor cells but not in untransformed cells. It was ascribed to a large protein complex identified as an extracellular form of proteasome 20S. Since circulating proteasome 20S has recently emerged as an important marker of tumor progression, the possibility of proteasomes controlling the production of angiostatic endostatin may inspire the development of new anticancer therapies. (AU)

• Processo FAPESP: 12/50191-4 - Síntese, estudo cinético e aplicações de substratos e inibidores de enzimas proteolíticas
• Beneficiário: Maria Aparecida Juliano
• Modalidade de apoio: Auxílio à Pesquisa - Temático