MCL-1-dependent leukemia cells are more sensitive to chemotherapy than BCL-2-dependent counterparts Export

@article{citeulike:6057741, abstract = {Myeloid cell leukemia sequence 1 (MCL-1) and B cell leukemia/lymphoma 2 (BCL-2) are anti-apoptotic proteins in the BCL-2 protein family often expressed in cancer. To compare the function of MCL-1 and BCL-2 in maintaining cancer survival, we constructed complementary mouse leukemia models based on E{micro}-Myc expression in which either BCL-2 or MCL-1 are required for leukemia maintenance. We show that the principal anti-apoptotic mechanism of both BCL-2 and MCL-1 in these leukemias is to sequester pro-death BH3-only proteins rather than BAX and BAK. We find that the MCL-1-dependent leukemias are more sensitive to a wide range of chemotherapeutic agents acting by disparate mechanisms. In common across these varied treatments is that MCL-1 protein levels rapidly decrease in a proteosome-dependent fashion, whereas those of BCL-2 are stable. We demonstrate for the first time that two anti-apoptotic proteins can enable tumorigenesis equally well, but nonetheless differ in their influence on chemosensitivity. 10.1083/jcb.200904049}, author = {Brunelle, Joslyn K. and Ryan, Jeremy and Yecies, Derek and Opferman, Joseph T. and Letai, Anthony}, citeulike-article-id = {6057741}, citeulike-linkout-0 = {http://dx.doi.org/10.1083/jcb.200904049}, citeulike-linkout-1 = {http://jcb.rupress.org/content/187/3/429.abstract}, citeulike-linkout-2 = {http://jcb.rupress.org/content/187/3/429.full.pdf}, day = {2}, doi = {10.1083/jcb.200904049}, journal = {J. Cell Biol.}, keywords = {antiapoptotic, bcl-2, brunel09pdf, family, leukemia, mcl-1, protein}, month = {November}, number = {3}, pages = {429--442}, posted-at = {2009-11-03 00:29:47}, priority = {2}, title = {MCL-1-dependent leukemia cells are more sensitive to chemotherapy than BCL-2-dependent counterparts}, url = {http://dx.doi.org/10.1083/jcb.200904049}, volume = {187}, year = {2009} }

TY - JOUR ID - citeulike:6057741 L3 - citeulike-article-id:6057741 N2 - Myeloid cell leukemia sequence 1 (MCL-1) and B cell leukemia/lymphoma 2 (BCL-2) are anti-apoptotic proteins in the BCL-2 protein family often expressed in cancer. To compare the function of MCL-1 and BCL-2 in maintaining cancer survival, we constructed complementary mouse leukemia models based on E{micro}-Myc expression in which either BCL-2 or MCL-1 are required for leukemia maintenance. We show that the principal anti-apoptotic mechanism of both BCL-2 and MCL-1 in these leukemias is to sequester pro-death BH3-only proteins rather than BAX and BAK. We find that the MCL-1-dependent leukemias are more sensitive to a wide range of chemotherapeutic agents acting by disparate mechanisms. In common across these varied treatments is that MCL-1 protein levels rapidly decrease in a proteosome-dependent fashion, whereas those of BCL-2 are stable. We demonstrate for the first time that two anti-apoptotic proteins can enable tumorigenesis equally well, but nonetheless differ in their influence on chemosensitivity. 10.1083/jcb.200904049 IS - 3 JF - J. Cell Biol. EP - 442 TI - MCL-1-dependent leukemia cells are more sensitive to chemotherapy than BCL-2-dependent counterparts VL - 187 SP - 429 KW - antiapoptotic KW - bcl-2 KW - brunel09pdf KW - family KW - leukemia KW - mcl-1 KW - protein AU - Brunelle, Joslyn AU - Ryan, Jeremy AU - Yecies, Derek AU - Opferman, Joseph AU - Letai, Anthony PY - 2009/11/02/ UR - http://dx.doi.org/10.1083/jcb.200904049 ER -