N. Liu, G. Caderas, C. Deillon, S. Hoffmann,
S. Klauser, T. Cui and B. Gutte
Revisiting
proteus: Do Minor Changes in Lectin Structure Matter in Biological Activity?
Lessons from and Potential Biotechnological Uses of the Diocleinae Subtribe
Lectins Pp.123-135
B. S. Cavada T. Barbosa, S. Arruda, T. B.
Grangeiro and M. Barral-Netto
Paolo Ascenzi, Luca Salvati, Martino
Bolognesi Marco Colasanti Fabio Polticelli and Giorgio Venturini
How
The Sequestration of a Protein Interferes with its Mechanism of Action: Example
of a New Family of Proteins Characterized
by a Particular Cysteine-Rich Carboxy-Terminal Domain Involved in Gene
Expression Regulation Pp.155-167
S.1 Thébault and J.M. Mesnard
Mif1:
A Missing Link between the Unfolded Protein Response Pathway and ER-Associated
Protein
Degradation?
Pp.169-190
Theo van Laar, Alex J. van der Eb and Carrol
Terleth
[Back
to top] Revisiting proteus: Do Minor Changes in Lectin Structure
Matter in Biological Activity? Lessons from and Potential Biotechnological Uses
of the Diocleinae Subtribe Lectins
B. S. Cavada T.
Barbosa, S. Arruda, T. B. Grangeiro and M. Barral-Netto
Significant differences in
function have been observed among lectins structurally similar to concanavalin
A, but their high homology with this widely used lectin has kept them in
obscurity. The observation of large differences in the potency of many of these
Diocleinae lectins as stimulators of Interferon-g production by human
peripheral blood mononuclear cells has lead to a major effort to unravel their
chemical structure and biological activity. Modeling studies of some of these
lectins reveal conformational changes in side chains of some residues involved
in the carbohydrate-binding site, with possible effects on the ability of these
proteins to recognize specific carbohydrate structures. Additionally, all them
constitute in fact a mixture of isolectins, which in different proportions
could lead to diverse effects. The present review of the biological actions of
Diocleinae lectins includes several in vitro and in vivo immunological
findings, as well as their effects on insect growth and reproduction. In these
systems Diocleinae lectins proved to be quite diverse in their potency. Such
diversity in the biological activity of highly related proteins recalls the
origin of the name protein: like Proteus, the capability of assuming various
forms is the essential feature of this class of molecules.
[Back
to top] Inhibition of Cysteine Protease Activity by NO-donors
Paolo Ascenzi, Luca Salvati, Martino
Bolognesi Marco Colasanti Fabio Polticelli and Giorgio Venturini
Cysteine proteases represent
a broad class of proteolytic enzymes widely distributed among living organisms.
Although well known as typical lysosomal enzymes, cysteine proteases are
actually recognized as multi-function enzymes, being involved in antigen
processing and presentation, in membrane-bound protein cleavage, as well as in
degradation of the cellular matrix and in processes of tissue remodeling. Very
recently, it has been shown that the NO(-donor)-mediated chemical modification
of the Cys catalytic residue of cysteine proteases, including Coxsackievirus
and Rhinovirus cysteine proteases, cruzain, Leishmania infantum cysteine protease,
falcipain, papain, as well as mammalian caspases, cathepsins and calpain,
blocks the enzyme activity in vitro and in vivo. Here, inhibition of
representative cysteine proteases by NO(-donors) is reviewed.
[Back to top] How The Sequestration of a Protein Interferes with its Mechanism of Action: Example of a New Family of Proteins Characterized by a Particular Cysteine-Rich Carboxy-Terminal Domain Involved in Gene Expression Regulation
S.1
Thébault and J.M. Mesnard
[Back
to top] Mif1: A Missing Link
between the Unfolded Protein Response Pathway and ER-Associated Protein
Degradation?
Eukaryotic cells have three
different mechanisms to deal with the accumulation of unfolded proteins in the
endoplasmic reticulum: (1) In cells in which unfolded polypeptides accumulate,
translation initiation is inhibited to prevent further accumulation of unfolded
proteins. (2) Expression of proteins involved in polypeptide folding is
strongly enhanced by a process called the Unfolded Protein Response (UPR). (3)
Proteins missing the proper tertiary structure are degraded by the
ER-Associated protein Degradation (ERAD) mechanism.
Recent studies in S.
cerevisiae have shown that the processes of UPR and ERAD are functionally
linked to each other. Cells lacking a functional ERAD show a constitutive
activation of UPR. In addition, many of the components of ERAD are under the
direct transcriptional control of UPR. Finally, while neither UPR nor ERAD are
essential for cell viability, deletion of both pathways results in severe
growth impairment.
UPR and ERAD are conserved
between yeast and mammalian cells. One of the components of mammalian UPR is
the protease presenilin-1. Mutations in the gene for presenilin-1 cause
early-onset familial Alzheimer’s disease. Interestingly, inhibition of
proteolysis by the ubiquitin-26S proteasome system has also been described for
Alzheimer’s disease. This suggests a link between UPR and ERAD in mammalian
cells.
The recently identified gene Mif1 is a possible candidate to form a direct link between UPR and ERAD in mammalian cells. The Mif1 gene is under the direct control of UPR. Mif1 is a trans-ER-membrane protein, with both the N- and the C-termini facing the cytoplasmic side of the ER membrane. It contains an N-terminal ubiquitin-like domain. It is anticipated that Mif1 may associate through its ubiquitin-like domain with the 26S proteasome, in this way connecting the protein degradation machinery to the ER membrane and resulting in an efficient ERAD.