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971.
972.
Foser S Redwanz I Ebeling M Heizmann CW Certa U 《Cellular and molecular life sciences : CMLS》2006,63(19-20):2387-2396
A hallmark of resistance to type I interferons (IFNs) is the lack of antiproliferative responses. We show here that costimulation with IFN-alpha and transforming growth factor beta-1 (TGF-beta) potentiates antiproliferative activity in a sensitive (ME15) and resistant (D10) human melanoma cell line. A DNA microarray-based search for proliferation control genes involved that are cooperatively activated by IFN-alpha and TGF-beta, yielded 28 genes. Among these are the insulin-like growth factor-binding protein 3 (IGFBP3) and the calcium-binding protein S100A2; we demonstrate, that recombinant IGFBP3 protein is a potent growth inhibitor requiring TGF-beta activity. The antiproliferative activity of S100A2 is significantly enhanced by IFN-alpha in stably transfected ME15 or D10 cell lines. We show for the first time that IFN-alpha is a potent inducer of intracellular calcium release required for activation of S100A2. Our study provides a functional link between IFN-alpha and TGF-beta signaling and extends the function of IFN signaling to calcium-sensitive processes. 相似文献
973.
Catassi A Cesario A Arzani D Menichini P Alama A Bruzzo C Imperatori A Rotolo N Granone P Russo P 《Cellular and molecular life sciences : CMLS》2006,63(19-20):2377-2386
The effects of different marine derived agents were studied in A549 cell growth. These drugs induced cell cycle arrest at the G2-M phase associated with the up-regulation of GADD45alpha-gamma and down-regulation of c-Myc. In treated cells, GADD45alpha-gamma and c-Myc were up- and down-regulated, respectively. A cascade of events leading to apoptotic mitochondrial 'intrinsic' pathway was observed in treated cells: (1) dephosphorylation of BAD serine136; (2) BAD dissociation from 14-3-3 followed by its association with BCL-XL; (3) cytochrome c release; (4) caspase-3 activation, and (5) cleavage of vimentin. Caspase(s) inhibitor prevented the formation of cleavage products and, in turn, apoptosis was inhibited through a p53-independent mechanism. Moreover, these compounds did not activate NF-kappaB. Our findings may offer new insights into the mechanisms of action of these agents in A549 cells. The better understanding of their effects might be important to fully exploit the potential of these new drugs. 相似文献
974.
975.
976.
Pahan K 《Cellular and molecular life sciences : CMLS》2006,63(10):1165-1178
Although a change in life-style is often the method of first choice for lipid lowering, lipid-lowering drugs, in general,
help to control elevated levels of different forms of lipids in patients with hyperlipidemia. While one group of drugs, statins,
lowers cholesterol, the other group, fibrates, is known to take care of fatty acids and triglycerides. In addition, other
drugs, such as ezetimibe, colesevelam, torcetrapib, avasimibe, implitapide, and niacin are also being considered to manage
hyperlipidemia. As lipids are very critical for cardiovascular diseases, these drugs reduce fatal and nonfatal cardiovascular
abnormalities in the general population. However, a number of recent studies indicate that apart from their lipidlowering
activities, statins and fibrates exhibit multiple functions to modulate intracellular signaling pathways, inhibit inflammation,
suppress the production of reactive oxygen species, and modulate T cell activity. Therefore, nowadays, these drugs are being
considered as possible therapeutics for several forms of human disorders including cancer, autoimmunity, inflammation, and
neurodegeneration. Here I discuss these applications in the light of newly discovered modes of action of these drugs.
Received 5 September 2005; received after revision 29 December 2005; accepted 26 January 2006 相似文献
977.
Phytanic acid is a branched-chain fatty acid that accumulates in a variety of metabolic disorders. High levels of phytanic
acid found in patients can exceed the millimolar range and lead to severe symptoms. Degradation of phytanic acid takes place
by α-oxidation inside the peroxisome. A deficiency of its breakdown, leading to elevated levels, can result from either a
general peroxisomal dysfunction or from a defect in one of the enzymes involved in α-oxidation. Research on Refsum disease,
belonging to the latter group of disorders and characterized by a deficiency of the first enzyme of α-oxidation, has extended
our knowledge of phytanic acid metabolism and pathology of the disease greatly over the past few decades. This review will
centre on this research on phytanic acid: its origin, the mechanism by which its α-oxidation takes place, its role in human
disease and the way it is produced from phytol.
Received 4 October 2005; received after revision 24 February 2006; accepted 26 April 2006 相似文献
978.
Mangold U 《Cellular and molecular life sciences : CMLS》2006,63(18):2095-2101
In contrast to the considerable interest in the oncogene ornithine decarboxylase (ODC) and in the family of antizymes with
regard to cell proliferation and tumorigenesis, the endogenous antizyme inhibitor (AZI) has been less well studied. AZI is
highly homologous to the enzyme ODC but does not possess any decarboxylase activity. Elevated ODC activity is associated with
most forms of human malignancies. Antizymes bind ODC, inhibit ODC activity and promote the ubiquitin-independent degradation
of ODC. Consequently they are proposed as tumor suppressors. In particular, the most studied member of the antizyme family,
antizyme 1, has been demonstrated to play a role in tumor suppression. AZI inactivates all members of the antizyme family,
reactivates ODC and prevents the proteolytic degradation of ODC, which may suggest a role for AZI in tumor progression.
Received 9 December 2005; received after revision 13 April 2006; accepted 1 June 2006 相似文献
979.
Myelin basic protein: a multifunctional protein 总被引:1,自引:1,他引:0
Boggs JM 《Cellular and molecular life sciences : CMLS》2006,63(17):1945-1961
Myelin basic protein (MBP), the second most abundant protein in central nervous system myelin, is responsible for adhesion
of the cytosolic surfaces of multilayered compact myelin. A member of the ‘intrinsically disordered’ or conformationally adaptable
protein family, it also appears to have several other functions. It can interact with a number of polyanionic proteins including
actin, tubulin, Ca2+-calmodulin, and clathrin, and negatively charged lipids, and acquires structure on binding to them. It may act as a membrane
actin-binding protein, which might allow it to participate in transmission of extracellular signals to the cytoskeleton in
oligodendrocytes and tight junctions in myelin. Some size isoforms of MBP are transported into the nucleus and thus they may
also bind polynucleotides. Extracellular signals received by myelin or cultured oligodendrocytes cause changes in phosphorylation
of MBP, suggesting that MBP is also involved in signaling. Further study of this very abundant protein will reveal how it
is utilized by the oligodendrocyte and myelin for different purposes.
Received 2 March 2006; received after revision 12 April 2006; accepted 16 May 2006 相似文献
980.
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