Tags

Type your tag names separated by a space and hit enter

Loss of the bcl-2 phosphorylation loop domain increases resistance of human leukemia cells (U937) to paclitaxel-mediated mitochondrial dysfunction and apoptosis.
Biochem Biophys Res Commun. 1999 May 27; 259(1):67-72.BB

Abstract

The impact of ectopic expression of an N-terminal phosphorylation loop deletant Bcl-2 protein (Bcl-2Delta32-80) on the response of U937 monoblastic leukemia cells to paclitaxel was examined. In contrast to recent findings in HL-60 cells (Fang et al., Cancer Res. 58, 3202, 1998), U937 cells overexpressing Bcl-2Delta32-80 were significantly more resistant than those overexpressing full-length protein to caspase-3 and -9 activation, PARP degradation, and apoptosis induced by paclitaxel (500 nM; 18 h). Bcl-2Delta32-80 was also more effective than its full-length counterpart in opposing paclitaxel-mediated mitochondrial dysfunction, e.g., loss of mitochondrial membrane potential (Deltapsim) and cytochrome c release into the cytoplasm. Enhanced resistance of U937/Bcl-2Delta32-80 cells to paclitaxel was observed primarily in the G2M population. Together, these findings demonstrate that deletion of the Bcl-2 phosphorylation loop domain increases resistance of U937 leukemia cells to paclitaxel-mediated mitochondrial damage and apoptosis and suggest that factors other than, or in addition to, phosphorylation contribute to Bcl-2-related cytoprotectivity against paclitaxel in this model system.

Authors+Show Affiliations

Department of Medicine, Virginia Commonwealth University, Richmond, Virginia, 23298, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10334917

Citation

Wang, S, et al. "Loss of the Bcl-2 Phosphorylation Loop Domain Increases Resistance of Human Leukemia Cells (U937) to Paclitaxel-mediated Mitochondrial Dysfunction and Apoptosis." Biochemical and Biophysical Research Communications, vol. 259, no. 1, 1999, pp. 67-72.
Wang S, Wang Z, Boise L, et al. Loss of the bcl-2 phosphorylation loop domain increases resistance of human leukemia cells (U937) to paclitaxel-mediated mitochondrial dysfunction and apoptosis. Biochem Biophys Res Commun. 1999;259(1):67-72.
Wang, S., Wang, Z., Boise, L., Dent, P., & Grant, S. (1999). Loss of the bcl-2 phosphorylation loop domain increases resistance of human leukemia cells (U937) to paclitaxel-mediated mitochondrial dysfunction and apoptosis. Biochemical and Biophysical Research Communications, 259(1), 67-72.
Wang S, et al. Loss of the Bcl-2 Phosphorylation Loop Domain Increases Resistance of Human Leukemia Cells (U937) to Paclitaxel-mediated Mitochondrial Dysfunction and Apoptosis. Biochem Biophys Res Commun. 1999 May 27;259(1):67-72. PubMed PMID: 10334917.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Loss of the bcl-2 phosphorylation loop domain increases resistance of human leukemia cells (U937) to paclitaxel-mediated mitochondrial dysfunction and apoptosis. AU - Wang,S, AU - Wang,Z, AU - Boise,L, AU - Dent,P, AU - Grant,S, PY - 1999/5/21/pubmed PY - 1999/5/21/medline PY - 1999/5/21/entrez SP - 67 EP - 72 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 259 IS - 1 N2 - The impact of ectopic expression of an N-terminal phosphorylation loop deletant Bcl-2 protein (Bcl-2Delta32-80) on the response of U937 monoblastic leukemia cells to paclitaxel was examined. In contrast to recent findings in HL-60 cells (Fang et al., Cancer Res. 58, 3202, 1998), U937 cells overexpressing Bcl-2Delta32-80 were significantly more resistant than those overexpressing full-length protein to caspase-3 and -9 activation, PARP degradation, and apoptosis induced by paclitaxel (500 nM; 18 h). Bcl-2Delta32-80 was also more effective than its full-length counterpart in opposing paclitaxel-mediated mitochondrial dysfunction, e.g., loss of mitochondrial membrane potential (Deltapsim) and cytochrome c release into the cytoplasm. Enhanced resistance of U937/Bcl-2Delta32-80 cells to paclitaxel was observed primarily in the G2M population. Together, these findings demonstrate that deletion of the Bcl-2 phosphorylation loop domain increases resistance of U937 leukemia cells to paclitaxel-mediated mitochondrial damage and apoptosis and suggest that factors other than, or in addition to, phosphorylation contribute to Bcl-2-related cytoprotectivity against paclitaxel in this model system. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/10334917/Loss_of_the_bcl_2_phosphorylation_loop_domain_increases_resistance_of_human_leukemia_cells__U937__to_paclitaxel_mediated_mitochondrial_dysfunction_and_apoptosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(99)90669-1 DB - PRIME DP - Unbound Medicine ER -