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BH3 profiling--measuring integrated function of the mitochondrial apoptotic pathway to predict cell fate decisions.
Del Gaizo Moore V, Letai A. Del Gaizo Moore V, et al. Among authors: letai a. Cancer Lett. 2013 May 28;332(2):202-5. doi: 10.1016/j.canlet.2011.12.021. Epub 2012 Jan 8. Cancer Lett. 2013. PMID: 22230093 Free PMC article. Review.
Apoptosis is a form of programmed cell death that is controlled at the mitochondrion by the BCL-2 family of proteins. While much has been learned about the structure and function of these proteins over the past two decades, the important goal of predicting cell fate decisi …
Apoptosis is a form of programmed cell death that is controlled at the mitochondrion by the BCL-2 family of proteins. While much has …
Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics.
Letai A, Bassik MC, Walensky LD, Sorcinelli MD, Weiler S, Korsmeyer SJ. Letai A, et al. Cancer Cell. 2002 Sep;2(3):183-92. doi: 10.1016/s1535-6108(02)00127-7. Cancer Cell. 2002. PMID: 12242151
These data support a two-class model for BH3 domains: BID-like domains that "activate" BAX, BAK and BAD-like domains that "sensitize" by occupying the pocket of antiapoptotic members....
These data support a two-class model for BH3 domains: BID-like domains that "activate" BAX, BAK and BAD-like domains that "sensitize" …
BH3 domains as BCL-2 inhibitors: prototype cancer therapeutics.
Letai A. Letai A. Expert Opin Biol Ther. 2003 Apr;3(2):293-304. doi: 10.1517/14712598.3.2.293. Expert Opin Biol Ther. 2003. PMID: 12662143
It is likely that most, if not all, cancer cells possess a mechanism for opposing programmed cell death, or apoptosis. One mechanism often used by cancer cells to escape apoptosis is the overexpression of B cell leukaemia/lymphoma-2 protein (BCL-2) or related antiapoptotic …
It is likely that most, if not all, cancer cells possess a mechanism for opposing programmed cell death, or apoptosis. One mechanism …
Antiapoptotic BCL-2 is required for maintenance of a model leukemia.
Letai A, Sorcinelli MD, Beard C, Korsmeyer SJ. Letai A, et al. Cancer Cell. 2004 Sep;6(3):241-9. doi: 10.1016/j.ccr.2004.07.011. Cancer Cell. 2004. PMID: 15380515
To test this, we generated mice expressing a conditional BCL-2 gene and constitutive c-myc that develop lymphoblastic leukemia. ...This suggests a generalizable model in which aberrations inherent to cancer generate tonic death signals that would otherwise kill the …
To test this, we generated mice expressing a conditional BCL-2 gene and constitutive c-myc that develop lymphoblastic leukemia. ...Th …
Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members.
Certo M, Del Gaizo Moore V, Nishino M, Wei G, Korsmeyer S, Armstrong SA, Letai A. Certo M, et al. Among authors: letai a. Cancer Cell. 2006 May;9(5):351-65. doi: 10.1016/j.ccr.2006.03.027. Cancer Cell. 2006. PMID: 16697956
We show that the antiapoptotic proteins BCL-2, BCL-XL, MCL-1, BFL-1, and BCL-w each bear a unique pattern of interaction with a panel of peptides derived from BH3 domains of BH3-only proteins. Cellular dependence on an antiapoptotic protein for survival can be decod …
We show that the antiapoptotic proteins BCL-2, BCL-XL, MCL-1, BFL-1, and BCL-w each bear a unique pattern of interaction with a
Restoring cancer's death sentence.
Letai A. Letai A. Cancer Cell. 2006 Nov;10(5):343-5. doi: 10.1016/j.ccr.2006.10.014. Cancer Cell. 2006. PMID: 17097553
Both groups find that expression of MCL-1, an antiapoptotic protein related to BCL-2, is a key determinant of resistance to ABT-737. ...Antagonism of BCL-2 is an exciting anticancer strategy that may soon become a clinical reality....
Both groups find that expression of MCL-1, an antiapoptotic protein related to BCL-2, is a key determinant of resistance to ABT-737. …
BH3 profiling identifies three distinct classes of apoptotic blocks to predict response to ABT-737 and conventional chemotherapeutic agents.
Deng J, Carlson N, Takeyama K, Dal Cin P, Shipp M, Letai A. Deng J, et al. Among authors: letai a. Cancer Cell. 2007 Aug;12(2):171-85. doi: 10.1016/j.ccr.2007.07.001. Cancer Cell. 2007. PMID: 17692808
Using a panel of 18 lymphoma cell lines, we show that a strategy we have developed, BH3 profiling, can identify apoptotic defects in cancer cells and separate them into three main classes based on position in the apoptotic pathway. ...
Using a panel of 18 lymphoma cell lines, we show that a strategy we have developed, BH3 profiling, can identify apoptotic defe …
Proapoptotic BH3-only BCL-2 family protein BIM connects death signaling from epidermal growth factor receptor inhibition to the mitochondrion.
Deng J, Shimamura T, Perera S, Carlson NE, Cai D, Shapiro GI, Wong KK, Letai A. Deng J, et al. Among authors: letai a. Cancer Res. 2007 Dec 15;67(24):11867-75. doi: 10.1158/0008-5472.CAN-07-1961. Cancer Res. 2007. PMID: 18089817
We show that EGFR activity is inhibited by erlotinib in H1650, a lung cancer cell line that bears a sensitizing EGFR mutation, but that H1650 is not killed. We identify the block in apoptosis in this cell line, and show that a novel form of erlotinib resistan …
We show that EGFR activity is inhibited by erlotinib in H1650, a lung cancer cell line that bears a sensitizing EGFR mutation, …
Diagnosing and exploiting cancer's addiction to blocks in apoptosis.
Letai AG. Letai AG. Nat Rev Cancer. 2008 Feb;8(2):121-32. doi: 10.1038/nrc2297. Nat Rev Cancer. 2008. PMID: 18202696 Review.
Such a determination can help predict not only whether cells are likely to be killed by antagonism of BCL2, but also whether they are likely to be sensitive to chemotherapy that kills by the intrinsic apoptotic pathway....
Such a determination can help predict not only whether cells are likely to be killed by antagonism of BCL2, but also whether they are …
Alteration of the mitochondrial apoptotic pathway is key to acquired paclitaxel resistance and can be reversed by ABT-737.
Kutuk O, Letai A. Kutuk O, et al. Among authors: letai a. Cancer Res. 2008 Oct 1;68(19):7985-94. doi: 10.1158/0008-5472.CAN-08-1418. Cancer Res. 2008. PMID: 18829556 Free PMC article.
Paclitaxel is a microtubule-targeting antineoplastic drug widely used in human cancers. Even when tumors are initially responsive, progression of disease despite continued taxane therapy is all too common in the treatment of many of the most common epithelial cancers, incl …
Paclitaxel is a microtubule-targeting antineoplastic drug widely used in human cancers. Even when tumors are initially responsive, pr …
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