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141.
Functions and pathologies of BiP and its interaction partners 总被引:1,自引:1,他引:0
J. Dudek J. Benedix S. Cappel M. Greiner C. Jalal L. Müller R. Zimmermann 《Cellular and molecular life sciences : CMLS》2009,66(9):1556-1569
The endoplasmic reticulum (ER) is involved in a variety of essential and interconnected processes in human cells, including
protein biogenesis, signal transduction, and calcium homeostasis. The central player in all these processes is the ER-lumenal
polypeptide chain binding protein BiP that acts as a molecular chaperone. BiP belongs to the heat shock protein 70 (Hsp70)
family and crucially depends on a number of interaction partners, including co-chaperones, nucleotide exchange factors, and
signaling molecules. In the course of the last five years, several diseases have been linked to BiP and its interaction partners,
such as a group of infectious diseases that are caused by Shigella toxin producing E. coli. Furthermore, the inherited diseases Marinesco-Sj?gren syndrome, autosomal dominant polycystic liver disease, Wolcott-Rallison
syndrome, and several cancer types can be considered BiP-related diseases. This review summarizes the physiological and pathophysiological
characteristics of BiP and its interaction partners.
Received 20 November 2008; received after revision 09 December 2008; accepted 12 December 2008 相似文献
142.
V. Le Fourn K. Gaplovska-Kysela B. Guhl R. Santimaria C. Zuber J. Roth 《Cellular and molecular life sciences : CMLS》2009,66(8):1434-1445
Little is known about the fate of machinery proteins of the protein quality control and endoplasmic reticulum(ER)-associated
degradation (ERAD). We investigated the degradation of the ERAD component EDEM1, which directs overexpressed misfolded glycoproteins
to degradation. Endogenous EDEM1 was studied since EDEM1 overexpression not only resulted in inappropriate occurrence throughout
the ER but also caused cytotoxic effects. Proteasome inhibitors had no effect on the clearance of endogenous EDEM1 in non-starved
cells. However, EDEM1 could be detected by immunocytochemistry in autophagosomes and biochemically in LC3 immuno-purified
autophagosomes. Furthermore, influencing the lysosome-autophagy pathway by vinblastine or pepstatin A/E64d and inhibiting
autophagosome formation by 3-methyladenine or ATGs short interfering RNA knockdown stabilized EDEM1. Autophagic degradation
involved removal of cytosolic Triton X-100-insoluble deglycosylated EDEM1, but not of EDEM1-containing ER cisternae. Our studies
demonstrate that endogenous EDEM1 in cells not stressed by the expression of a transgenic misfolded protein reaches the cytosol
and is degraded by basal autophagy.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 15 January 2009; received after revision 16 February 2009; accepted 17 February 2009
V. Le Fourn, K. Gaplovska-Kysela: These authors equally contributed to this work. 相似文献
143.
Berger W Steiner E Grusch M Elbling L Micksche M 《Cellular and molecular life sciences : CMLS》2009,66(1):43-61
The unique and evolutionary highly conserved major vault protein (MVP) is the main component of ubiquitous, large cellular
ribonucleoparticles termed vaults. The 100 kDa MVP represents more than 70% of the vault mass which contains two additional
proteins, the vault poly (ADP-ribose) polymerase (vPARP) and the telomerase-associated protein 1 (TEP1), as well as several
short untranslated RNAs (vRNA). Vaults are almost ubiquitously expressed and, besides chemotherapy resistance, have been implicated
in the regulation of several cellular processes including transport mechanisms, signal transmissions and immune responses.
Despite a growing amount of data from diverse species and systems, the definition of precise vault functions is still highly
complex and challenging. Here we review the current knowledge on MVP and vaults with focus on regulatory functions in intracellular
signal transduction and immune defence.
Received 27 June 2008; received after revision 25 July 2008; accepted 30 July 2008 相似文献
144.
145.
Betaine homocysteine S-methyltransferase: just a regulator of homocysteine metabolism? 总被引:1,自引:0,他引:1
Betaine homocysteine methyltransferase (BHMT), a Zn2+-dependent thiolmethyltransferase, contributes to the regulation of homocysteine levels, increases in which are considered
a risk factor for cardiovascular diseases. Most plasma homocysteine is generated through the liver methionine cycle, in which
BHMT metabolizes approximately 25% of this non-protein amino acid. This process allows recovery of one of the three methylation
equivalents used in phosphatidylcholine synthesis through transmethylation, a major homocysteine-producing pathway. Although
BHMT has been known for over 40 years, the difficulties encountered in its isolation precluded detailed studies until very
recently. Thus, the last 10 years, since the sequence became available, have yielded extensive structural and functional data.
Moreover, recent findings offer clues for potential new functions for BHMT. The purpose of this review is to provide an integrated
view of the knowledge available on BHMT, and to analyze its putative roles in other processes through interactions uncover
to date.
Received 26 May 2006; received after revision 3 July 2006; accepted 24 August 2006 相似文献
146.
Expansion of amino acid homo-sequences, such as polyglutamines or polyalanines, in proteins has been directly implicated in
various degenerative diseases through a mechanism of protein misfolding and aggregation. However, it is still unclear how
the nature of the expansion and the protein context influence the tendency of a protein to aggregate. Here, we have addressed
these questions using spinocerebellar ataxia type-3 (ATX3) protein, the best characterised of the polyglutamine proteins,
chosen as a model system. Using a transfected mammalian cell line, we demonstrate that ATX3 aggregation is noticeably reduced
by deletion or replacement of regions other than the polyglutamine tract. The nature of the amino acid homo-sequences also
has a strong influence on aggregation. From our studies, we draw general conclusions on the effect of the protein architecture
and of the amino acid homo-sequence on pathology.
Received 3 March 2006; received after revision 19 April 2006; accepted 22 May 2006 相似文献
147.
Glycogen synthase kinase 3β and Alzheimer’s disease: pathophysiological and therapeutic significance 总被引:3,自引:0,他引:3
Balaraman Y Limaye AR Levey AI Srinivasan S 《Cellular and molecular life sciences : CMLS》2006,63(11):1226-1235
Alzheimer’s disease (AD) is a neurodegenerative disorder associated with cognitive and behavioral dysfunction and is the leading
cause of dementia in the elderly. Several studies have implicated molecular and cellular signaling cascades involving the
serine-threonine kinase, glycogen synthase kinase β(GSK-3β) in the pathogenesis of AD. GSK-3β may play an important role in
the formation of neurofibrillary tangles and senile plaques, the two classical pathological hallmarks of AD. In this review,
we discuss the interaction between GSK-3β and several key molecules involved in AD, including the presenilins, amyloid precursor
protein, tau, and β-amyloid. We identify the signal transduction pathways involved in the pathogenesis of AD, including Wnt,
Notch, and the PI3 kinase/Akt pathway. These may be potential therapeutic targets in AD.
Received 19 December 2005; received after revision 24 January 2006; accepted 6 February 2006 相似文献
148.
Based on the classification of bacterial lipolytic enzymes, family I.3 lipase is a member of the large group of Gram-negative
bacterial true lipases. This lipase family is distinguished from other families not only by the amino acid sequence, but also
by the secretion mechanism. Lipases of family I.3 are secreted via the well-known type I secretion system. Like most of proteins
secreted via this system, family I.3 lipases are composed of two domains with distinct yet related functions. Recent years
have seen an increasing amount of research on this lipase family, in terms of isolation, secretion mechanism, as well as biochemical
and biophysical studies. This review describes our current knowledge on the structure-function relationships of family I.3
lipase, with an emphasis on its secretion mechanism.
Received 18 April 2006; received after revision 3 July 2006; accepted 24 August 2006 相似文献
149.
Niimura N Arai S Kurihara K Chatake T Tanaka I Bau R 《Cellular and molecular life sciences : CMLS》2006,63(3):285-300
Neutron diffraction provides an experimental method of directly locating hydrogen atoms in proteins, a technique complimentary to ultra-high-resolution [1, 2] X-ray diffraction. Three different types of neutron diffractometers for biological macromolecules have been constructed in Japan, France and the United States, and they have been used to determine the crystal structures of proteins up to resolution limits of 1.5-2.5 A. Results relating to hydrogen positions and hydration patterns in proteins have been obtained from these studies. Examples include the geometrical details of hydrogen bonds, H/D exchange in proteins and oligonucleotides, the role of hydrogen atoms in enzymatic activity and thermostability, and the dynamical behavior of hydration structures, all of which have been extracted from these structural results and reviewed. Other techniques, such as the growth of large single crystals, the preparation of fully deuterated proteins, the use of cryogenic techniques, and a data base of hydrogen and hydration in proteins, will be described. 相似文献
150.
Lubelski J Rink R Khusainov R Moll GN Kuipers OP 《Cellular and molecular life sciences : CMLS》2008,65(3):455-476
This review discusses the state-of-the-art in molecular research on the most prominent and widely applied lantibiotic, i.e., nisin. The developments in understanding its complex biosynthesis and mode of action are highlighted. Moreover, novel applications
arising from engineering either nisin itself, or from the construction of totally novel dehydrated and/or lanthionine-containing
peptides with desired bioactivities are described. Several challenges still exist in understanding the immunity system and
the unique multiple reactions occurring on a single substrate molecule, carried out by the dehydratase NisB and the cyclization
enzyme NisC. The recent elucidation of the 3-D structure of NisC forms the exciting beginning of further 3-D-structure determinations
of the other biosynthetic enzymes, transporters and immunity proteins. Advances in achieving in vitro activities of lanthionine-forming enzymes will greatly enhance our understanding of the molecular characteristics of the
biosynthesis process, opening up new avenues for developing unique and novel biocatalytic processes.
Received 9 April 2007; received after revision 31 August 2007; accepted 28 September 2007 相似文献