This laboratory belongs to the
Department of Biochemistry and Molecular Biology from the Universidad
de
Oviedo, and to the Instituto Universitario de Oncología del
Principado de
Asturias (IUOPA). The main focus of this lab is the identification and
characterization of proteolytic enzymes involved in human pathologies,
with special relevance in those implicated in cancer growth and
progression. During the last 12 years this laboratory has identified
more than 60 human proteases from different catalytic classes,
including
matrix metalloproteases (MMPs), 8 members of the ADAMTS family (A
Disintegrin And Metalloprotease with Thrombospondin domains), cysteine
proteases from the cathepsin family, the ubiquitin-specific proteases
and the recently identified family
of autophagins, implicated in death by autophagy. Other proteases
include FACE-1 and FACE-2, involved in the maturation of prenylated
proteins as members of the Ras family of oncogenes, and several serine
proteases expressed by human carcinomas.
In order to understand the biological function of proteases, we
have
also characterized several proteases from different model organisms,
including mouse, Caenorhabditis
elegans, Drosophila
melanogaster or Arabidopsis
thaliana. The studies with knockout animals has allowed us to
better understand the function of these proteolytic enzymes, and has
contributed to the identification of the biological substrates of some
of these proteases. Recent works from our lab have allowed us to
identify lamin A as the main substrate of FACE-1, a metalloprotease
that catalyzes the cleavage of the three C-terminal residues of
farnesylated proteins. Our work with animal models has allowed us to
identify proteases as key regulatory components during the initial
steps of carcinogenesis. In this sense, specific deletion of the
neutrophil collagenase (MMP8) gene in mouse results in increased
susceptibility to skin tumors in mice, suggesting a protective role for
MMPs in cancer development.
The recent availability of the human, mouse and rat genomic
sequences
has
allowed us to classify a total of 561 human, 641 mouse and 626 rat
protese
genes,
that represents about 1.7% of the genes encoded by these organisms.
Similar to the increased number of protease genes in rodents, the
protease inhibitor complement is also more complex in rodents (183 in
rat and 199 in mouse) than in human (156). These data suggests that the
increase in proteolytic activity in rodents has been compensated by an
increased in the number of protease inhibitor genes in these organisms.
Although this number is expected to grow in the near future, as genomic
gaps are closed and novel proteolytic activities are discovered, this
study represents the first glimpse at the human and mouse genomes
through the study of a diverse family of enzymes comprising almost 2%
of
both genomes.
For problems or suggestions, please write to Xose S Puente