Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q07644 (polypeptide)
 72,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously demonstrated that sonic extracts of Fusobacterium nucleatum FDC 364 were capable of inhibiting human T-cell responses to mitogens and antigens. The purified F. nucleatum immunosuppressive protein (FIP) is composed of two subunits of 44 and 48 kDa. Furthermore, FIP inhibits T-cell activation by arresting cells in the middle of the G(1) phase of the cell cycle; the data available to date suggest that FIP impairs the expression of the proliferating-cell nuclear antigen. To initiate delineation of FIP structure-function relationships, molecular cloning of the FIP gene was carried out. A DNA library of F. nucleatum FDC 364 was constructed by partial digestion of genomic DNA with Sau3A and screened for the production of FIP with polyclonal antibody. Twelve immunoreactive clones were identified. One of these clones contained a 3.1-kbp insert and was chosen for further study. Cell lysates were found to contain an immunoreactive band that comigrated with the 44-kDa subcomponent of the native FIP. Sequencing of the 3.1-kpb insert revealed the presence of three open reading frames (ORFs). One ORF extends from nucleotides 415 to 1620, encodes 402 amino acids, and is preceded by a ribosome-binding site. Deletion analysis and antibody elution analysis showed that this ORF encodes the 44-kDa subunit (FipA) of native FIP. A second ORF is situated upstream of fipA. However, Northern (RNA) analysis suggested that fipA is not transcribed as part of an operon but transcribed from its own promotor. Finally, the partially purified recombinant FipA protein was capable of impairing T-cell activation in a manner consistent with the native protein. These results indicate that the two components that form the native protein are most probably distinct gene products and suggest that the 44-kDa FipA polypeptide is sufficient to mediate the immunosuppressive activities of the native protein complex.
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PMID:Identification and analysis of fipA, a Fusobacterium nucleatum immunosuppressive factor gene. 860 98

The adenosine triphosphate binding-site-directed agent STI571 and the tyrphostin adaphostin are undergoing evaluation as bcr/abl kinase inhibitors. The current study compared the effects of these agents on the survival of K562 cells, bcr/abl-transduced FDC-P1 cells, and myeloid progenitors from patients with chronic myelogenous leukemia (CML) compared with healthy donors. Treatment of K562 cells with 10 microM adaphostin resulted in decreased p210(bcr/abl) polypeptide levels in the first 6 hours, followed by caspase activation and accumulation of apoptotic cells in less than 12 hours. By 24 hours, 90% of the cells were apoptotic and unable to form colonies. In contrast, 20 microM STI571 caused rapid inhibition of bcr/abl autophosphorylation without p210(bcr/abl) degradation. Although this was followed by the inhibition of Stat5 phosphorylation and the down-regulation of Bcl-x(L) and Mcl-1, only 7% +/- 3% and 25% +/- 9% of cells were apoptotic at 16 and 24 hours, respectively. Instead, the cytotoxic effects of STI571 became more pronounced with prolonged exposure, with IC90 values greater than 20 microM and 1.0 +/- 0.6 microM after 24 and 48 hours, respectively. Consistent with these results, 24-hour adaphostin exposure inhibited CML granulocyte colony-forming units (CFU-G) (median IC50, 12 microM) but not normal CFU-G (median IC50, greater than 20 microM), whereas 24-hour STI571 treatment had no effect on CML or normal CFU-G. Additional experiments revealed that STI571-resistant K562 cells remained sensitive to adaphostin. Moreover, the combination of STI571 + adaphostin induced more cytotoxicity in K562 cells and in CML CFU-G than either agent alone did. Collectively, these results identify adaphostin as a mechanistically distinct CML-selective agent that retains activity in STI571-resistant cell lines.
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PMID:Effects of the Bcr/abl kinase inhibitors STI571 and adaphostin (NSC 680410) on chronic myelogenous leukemia cells in vitro. 1178 Dec 52


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