Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The BCR-ABL fusion protein with strong tyrosine kinase activity is one of the molecular biological bases of leukemia. Imatinib (Gleevec), a specific targeted drug for the treatment of chronic myeloid leukemia (CML), was developed for inhibiting the kinase activity of the BCR-ABL fusion protein. Despite the positive clinical efficacy of imatinib, the proportion of imatinib resistance has gradually increased. The main reason for the resistance is a decrease in sensitivity to imatinib caused by mutation or amplification of the BCR-ABL gene. In response to this phenomenon, the new generation of tyrosine kinase inhibitors (TKIs) targeting the BCR-ABL fusion protein was developed to solve the problem. However this strategy only selectively inhibits the tyrosine kinase activity of the BCR-ABL protein without eliminating the BCR-ABL protein, it does not fundamentally cure the BCR-ABL-positive leukemia patients. With the accumulation of the knowledge of cellular molecular biology, it has become possible to specifically eliminate certain proteins by cellular proteases in a specific way. Therefore, the therapeutic strategy to induce the degradation of the BCR-ABL fusion protein is superior to the strategy of inhibiting its activity. The protein degradation strategy is also a solution to the TKI resistance caused by different BCR-ABL gene point mutations. In order to provide possible exploration directions and clues for eliminating the BCR-ABL fusion protein in tumor cells, we summarize the significant molecules involved in the degradation pathway of the BCR-ABL protein, as well as the reported potent compounds that can target the BCR-ABL protein for degradation.
 ...
PMID:Regulatory Molecules and Corresponding Processes of BCR-ABL Protein Degradation. 3125 55

Imatinib (IM) is successfully used in the majority of patients with chronic myeloid leukemia (CML), but some patients develop resistance to drug treatment. Insufficient apoptosis results in uncontrolled cell proliferation, which is closely associated with the occurrence of drug resistance. Therefore, it is crucial to identify new biomarkers related to drug resistance. This aim of the present study was to investigate the profile of apoptosis-related proteins in K562 and K562/G (IM-resistant K562 cells) cells, in order to identify new biomarkers. A human apoptosis antibody array was used to screen 46 proteins in the two cells lines, among which 20 proteins were found to be differentially expressed between K562 and K562/G cells. The major proteins included secreted caspase-8, insulin-like growth factor-binding protein (IGFBP)-1, IGFBP-2, IGFBP-3, caspase-3 and p27. IGFBP-1 IGFBP-2 and IGFBP-3 were selected for the follow-up study. Subsequently, reverse transcription-quantitative PCR analysis and western blotting were used to detect the expression levels of the IGFBPs. The results revealed that the expression levels of IGFBP-2 and IGFBP-3 in K562/G cells were significantly decreased compared with those in K562 cells, whereas the IGFBP-1 level was higher. Moreover, no significant correlation was observed between IGFBP-1 or IGFBP-2 and the level of the BCR-ABL fusion protein, whereas decreasing IGFBP-3 levels were associated with increasing BCR-ABL levels. These results suggested that IGFBP-1, IGFBP-2 and IGFBP-3 could be useful novel biomarkers for IM resistance in CML.
 ...
PMID:Insulin-like growth factor-binding proteins play a significant role in the molecular response to imatinib in chronic myeloid leukemia patients. 3210 32


<< Previous 1 2 3 4 5 6 7