Linked Life Data

9103470

Source:http://linkedlifedata.com/resource/pubmed/id/9103470

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1997-5-5
pubmed:abstractText
Undecylprodigiosin (UP) is the first described member of a family of related compounds showing immunosuppressive activity. We have investigated the biological effect and mechanism of action of UP in human lymphocytes. We show that UP blocks the proliferation of purified peripheral human T and B lymphocytes with an IC50 of 3 to 8 ng/ml and following stimulation by all mitogens used, with no effect on cell death. At the concentrations active on fresh lymphocytes, UP has no significant effect on the proliferation of different leukemic cell lines. UP blocks T cell activation in mid to late G1 phase and before entry into S phase, as shown by analysis of the cell cycle and of the expression of c-myc, IL-2, transferrin receptor, and B-myb. UP inhibits only partially the expression of IL-2R, suggesting that the major target of UP is localized downstream from the interaction between IL-2 and its receptor. The expression of cell cycle genes was investigated. The phosphorylation of the retinoblastoma protein was completely blocked by UP, an event alone sufficient to explain the block of S phase entry and the inhibition of proliferation. The induction of cyclin D2 and the decrease in p27 were not inhibited by UP, whereas the induction of cyclin E, cyclin A, cyclin-dependent kinase-2, and cyclin-dependent kinase-4 was strongly inhibited, potentially explaining the inhibition of retinoblastoma protein phosphorylation. These data clearly show that the site of action of UP is different from that of both cyclosporin A and rapamycin, and that this new class of compounds may, therefore, be good candidates for combined therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CDC2-CDC28 Kinases, http://linkedlifedata.com/resource/pubmed/chemical/CDK2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/CDK4 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 2, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 4, http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Immunosuppressive Agents, http://linkedlifedata.com/resource/pubmed/chemical/Prodigiosin, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Retinoblastoma Protein, http://linkedlifedata.com/resource/pubmed/chemical/undecylprodigiosin
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
158
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3987-95
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Characterization of the new immunosuppressive drug undecylprodigiosin in human lymphocytes: retinoblastoma protein, cyclin-dependent kinase-2, and cyclin-dependent kinase-4 as molecular targets.
pubmed:affiliation
Department of Immunology and Cell Biology, Institute of Pharmacological Research Mario Negri, Milan, Italy.
pubmed:publicationType
Journal Article