Pub. Date : 2004 May 1
PMID : 15093752
6 Functional Relationships(s)Download |
Sentence | Compound Name | Protein Name | Organism |
| 1 | The hierarchical relationship between MAPK signaling and ROS generation in human leukemia cells undergoing apoptosis in response to the proteasome inhibitor Bortezomib. | Bortezomib | mitogen-activated protein kinase 3 | Homo sapiens |
| 2 | Treatment of Jurkat or U937 cells with Bortezomib resulted in activation of c-Jun-N-terminal kinase (JNK) and p38 MAPK (mitogen-activated protein kinase), inactivation of extracellular signal-regulating kinase 1/2 (ERK1/2), cytochrome c release, caspase-9, -3, and -8 activation, and apoptosis. | Bortezomib | mitogen-activated protein kinase 3 | Homo sapiens |
| 3 | Inducible expression of a constitutively active MEK1 construct blocked Bortezomib-mediated ERK1/2 inactivation, significantly attenuated Bortezomib lethality, and unexpectedly prevented JNK activation. | Bortezomib | mitogen-activated protein kinase 3 | Homo sapiens |
| 4 | Conversely, pharmacologic MEK/ERK1/2 inhibition promoted Bortezomib-mediated JNK activation and apoptosis. | Bortezomib | mitogen-activated protein kinase 3 | Homo sapiens |
| 5 | Together, these findings suggest that in human leukemia cells, Bortezomib-induced oxidative injury operates at a proximal point in the cell death cascade to antagonize cytoprotective ERK1/2 signaling, promote activation of the stress-related JNK pathway, and to trigger mitochondrial dysfunction, caspase activation, and apoptosis. | Bortezomib | mitogen-activated protein kinase 3 | Homo sapiens |
| 6 | They also suggest the presence of a feedback loop wherein Bortezomib-mediated ERK1/2 inactivation contributes to JNK activation, thereby amplifying the cell death process. | Bortezomib | mitogen-activated protein kinase 3 | Homo sapiens |