Genomes and Genes
Gene Symbol: Mcl-1
Description: MCL1, BCL2 family apoptosis regulator
Alias: BCL2L3, EAT, MCL1-ES, MCL1L, MCL1S, Mcl-1, bcl2-L-3, mcl1/EAT, induced myeloid leukemia cell differentiation protein Mcl-1, BCL2 family apoptosis regulator, bcl-2-like protein 3, bcl-2-related protein EAT/mcl1, myeloid cell leukemia 1, myeloid cell leukemia ES, myeloid cell leukemia sequence 1 (BCL2-related)
- Schulze Bergkamen H, Ehrenberg R, Hickmann L, Vick B, Urbanik T, Schimanski C, et al. Bcl-x(L) and Myeloid cell leukaemia-1 contribute to apoptosis resistance of colorectal cancer cells. World J Gastroenterol. 2008;14:3829-40 pubmed..Our data suggest that Bcl-x(L) and, to a lower extent, Mcl-1, are important anti-apoptotic factors in CRC. Specific downregulation of Bcl-x(L) is a promising approach to sensitize CRC cells towards chemotherapy and targeted therapy. ..
- Akgul C. Mcl-1 is a potential therapeutic target in multiple types of cancer. Cell Mol Life Sci. 2009;66:1326-36 pubmed publisher..This review summarizes the current knowledge on the regulation of Mcl-1 expression and discusses the alternative approaches targeting Mcl-1 in human cancer cells whose survivals mainly depend on Mcl-1. ..
- Lynch J, Rajendran R, Xenaki G, Berrou I, Demonacos C, Krstic Demonacos M. The role of glucocorticoid receptor phosphorylation in Mcl-1 and NOXA gene expression. Mol Cancer. 2010;9:38 pubmed publisher..Our results provide molecular base and valuable knowledge for improving the GC based therapies of leukaemia. ..
- Awan F, Kay N, Davis M, Wu W, Geyer S, Leung N, et al. Mcl-1 expression predicts progression-free survival in chronic lymphocytic leukemia patients treated with pentostatin, cyclophosphamide, and rituximab. Blood. 2009;113:535-7 pubmed publisher..Because the trials described were conducted before the requirement to register them was implemented, they are not registered in a clinical trial database.). ..
- Wei G, Margolin A, Haery L, Brown E, Cucolo L, Julian B, et al. Chemical genomics identifies small-molecule MCL1 repressors and BCL-xL as a predictor of MCL1 dependency. Cancer Cell. 2012;21:547-62 pubmed publisher..A computational model, validated in vivo, indicated that high BCL-xL expression confers resistance to MCL1 repression, thereby identifying a patient-selection strategy for the clinical development of MCL1 inhibitors. ..
- Dehan E, Bassermann F, Guardavaccaro D, Vasiliver Shamis G, Cohen M, Lowes K, et al. betaTrCP- and Rsk1/2-mediated degradation of BimEL inhibits apoptosis. Mol Cell. 2009;33:109-16 pubmed publisher..Our findings reveal that betaTrCP promotes cell survival in cooperation with the ERK-RSK pathway by targeting BimEL for degradation. ..
- Liu Q, Moldoveanu T, Sprules T, Matta Camacho E, Mansur Azzam N, Gehring K. Apoptotic regulation by MCL-1 through heterodimerization. J Biol Chem. 2010;285:19615-24 pubmed publisherb>Myeloid cell leukemia 1 (MCL-1), an anti-apoptotic BCL-2 family member active in the preservation of mitochondrial integrity during apoptosis, has fundamental roles in development and hematopoiesis and is dysregulated in human cancers...
- Germain M, Nguyen A, Le Grand J, Arbour N, Vanderluit J, Park D, et al. MCL-1 is a stress sensor that regulates autophagy in a developmentally regulated manner. EMBO J. 2011;30:395-407 pubmed publisher..Our results define a pathway whereby MCL-1 has a key role in determining cell fate, by coordinately regulating apoptosis and autophagy. ..
- Simonin K, Brotin E, Dufort S, Dutoit S, Goux D, N Diaye M, et al. Mcl-1 is an important determinant of the apoptotic response to the BH3-mimetic molecule HA14-1 in cisplatin-resistant ovarian carcinoma cells. Mol Cancer Ther. 2009;8:3162-70 pubmed publisher..BH3-mimetic compounds represent promising tools for this purpose either on their own (direct or indirect pan-inhibitors) or in combination with new drugs aiming to inactivate Mcl-1. ..
- Edlich F, Banerjee S, Suzuki M, Cleland M, Arnoult D, Wang C, et al. Bcl-x(L) retrotranslocates Bax from the mitochondria into the cytosol. Cell. 2011;145:104-16 pubmed publisher..We propose that Bcl-x(L) inhibits and maintains Bax in the cytosol by constant retrotranslocation of mitochondrial Bax. ..
- Rahmani M, Davis E, Bauer C, Dent P, Grant S. Apoptosis induced by the kinase inhibitor BAY 43-9006 in human leukemia cells involves down-regulation of Mcl-1 through inhibition of translation. J Biol Chem. 2005;280:35217-27 pubmed..Together, these findings demonstrate that BAY 43-9006 mediates cell death in human leukemia cells, at least in part, through down-regulation of Mcl-1 via inhibition of translation. ..
- Brotin E, Meryet Figuière M, Simonin K, Duval R, Villedieu M, Leroy Dudal J, et al. Bcl-XL and MCL-1 constitute pertinent targets in ovarian carcinoma and their concomitant inhibition is sufficient to induce apoptosis. Int J Cancer. 2010;126:885-95 pubmed publisher..Therefore, Bcl-X(L) and MCL-1 targeted strategies could constitute an efficient therapeutic tool for the treatment of chemoresistant ovarian carcinoma, in association with conventional chemotherapy. ..
- Xu H, Jiang B, Meng L, Ren T, Zeng Y, Wu J, et al. N-?-acetyltransferase 10 protein inhibits apoptosis through RelA/p65-regulated MCL1 expression. Carcinogenesis. 2012;33:1193-202 pubmed publisher..These results indicate that Naa10p inhibits apoptosis through Naa10p-RelA/p65-dependent MCL1 transcriptional activation. ..
- Nagata M, Wada K, Nakajima A, Nakajima N, Kusayama M, Masuda T, et al. Role of myeloid cell leukemia-1 in cell growth of squamous cell carcinoma. J Pharmacol Sci. 2009;110:344-53 pubmed..These results imply a potentially important and novel role of the inhibition of Mcl-1 function by the use of specific siRNA in the treatment of SCC...
- Lowman X, McDonnell M, Kosloske A, Odumade O, Jenness C, Karim C, et al. The proapoptotic function of Noxa in human leukemia cells is regulated by the kinase Cdk5 and by glucose. Mol Cell. 2010;40:823-33 pubmed publisher..We propose that Noxa plays both growth-promoting and proapoptotic roles in hematopoietic cancers with phospho-S(13) as the glucose-sensitive toggle switch controlling these opposing functions. ..
- Pearce A, Lyles D. Vesicular stomatitis virus induces apoptosis primarily through Bak rather than Bax by inactivating Mcl-1 and Bcl-XL. J Virol. 2009;83:9102-12 pubmed publisher..Similarly, treatment with an inhibitor of caspase-8 inhibited VSV-induced apoptosis. These results indicate a role for cross talk from the death receptor pathway in the activation of the mitochondrial pathway by VSV. ..
- Cheng Y, Lee H, Shiau M, Wu T, Huang T, Chang Y. Human papillomavirus type 16/18 up-regulates the expression of interleukin-6 and antiapoptotic Mcl-1 in non-small cell lung cancer. Clin Cancer Res. 2008;14:4705-12 pubmed publisher..The involvement of HPV infection in lung tumorigenesis may be partly through a concomitant increased expression of autocrine and/or paracrine IL-6 and the downstream Mcl-1. ..
- Kazi A, Sun J, Doi K, Sung S, Takahashi Y, Yin H, et al. The BH3 alpha-helical mimic BH3-M6 disrupts Bcl-X(L), Bcl-2, and MCL-1 protein-protein interactions with Bax, Bak, Bad, or Bim and induces apoptosis in a Bax- and Bim-dependent manner. J Biol Chem. 2011;286:9382-92 pubmed publisher..Finally, BH3-M6 sensitizes cells to apoptosis induced by the proteasome inhibitor CEP-1612. ..
- Allen T, Zhu C, Jones K, Yanagawa N, Tsao M, Bishop J. Interaction between MYC and MCL1 in the genesis and outcome of non-small-cell lung cancer. Cancer Res. 2011;71:2212-21 pubmed publisher..Our findings therefore produce a convergence of mouse and human results that explain how MCL1 can block an important negative consequence of MYC overexpression in both experimental models and clinical cases of NSCLC. ..
- Zhai D, Jin C, Huang Z, Satterthwait A, Reed J. Differential regulation of Bax and Bak by anti-apoptotic Bcl-2 family proteins Bcl-B and Mcl-1. J Biol Chem. 2008;283:9580-6 pubmed publisher..Altogether, the findings reveal striking distinctions in the behaviors of Bcl-B and Mcl-1 relative to the other anti-apoptotic Bcl-2 family members, where Bcl-B and Mcl-1 display reciprocal abilities to bind and neutralize Bax and Bak. ..
- Schwickart M, Huang X, Lill J, Liu J, Ferrando R, French D, et al. Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival. Nature. 2010;463:103-7 pubmed publisher..These results identify USP9X as a prognostic and therapeutic target, and they show that deubiquitinases may stabilize labile oncoproteins in human malignancies. ..
- Meng X, Lee S, Dai H, Loegering D, Yu C, Flatten K, et al. Mcl-1 as a buffer for proapoptotic Bcl-2 family members during TRAIL-induced apoptosis: a mechanistic basis for sorafenib (Bay 43-9006)-induced TRAIL sensitization. J Biol Chem. 2007;282:29831-46 pubmed..Collectively, these observations not only suggest a model in which Mcl-1 confers TRAIL resistance by serving as a buffer for Bak, Bim, and Puma, but also identify sorafenib as a potential modulator of TRAIL sensitivity...
- Cheng S, Gao N, Zhang Z, Chen G, Budhraja A, Ke Z, et al. Quercetin induces tumor-selective apoptosis through downregulation of Mcl-1 and activation of Bax. Clin Cancer Res. 2010;16:5679-91 pubmed publisher..To investigate the in vivo antitumor efficacy of quercetin in U937 xenografts and the functional roles of Mcl-1 and Bax in quercetin-induced apoptosis in human leukemia...
- Clohessy J, Zhuang J, de Boer J, Gil Gomez G, Brady H. Mcl-1 interacts with truncated Bid and inhibits its induction of cytochrome c release and its role in receptor-mediated apoptosis. J Biol Chem. 2006;281:5750-9 pubmed..Therefore, our study demonstrates a novel regulation of tBid by Mcl-1 through protein-protein interaction in apoptotic signaling from death receptors to mitochondria. ..
- Boisvert Adamo K, Longmate W, Abel E, Aplin A. Mcl-1 is required for melanoma cell resistance to anoikis. Mol Cancer Res. 2009;7:549-56 pubmed publisher..Together, these data support the notion that BH3 mimetic compounds that target Mcl-1 may be effective for the treatment of melanoma in combinatorial strategies with agents that disrupt fibronectin-integrin signaling. ..
- Inuzuka H, Shaik S, Onoyama I, Gao D, Tseng A, Maser R, et al. SCF(FBW7) regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction. Nature. 2011;471:104-9 pubmed publisher..Therefore, our work provides insight into the molecular mechanism of direct tumour suppression by FBW7 and has implications for the targeted treatment of patients with FBW7-deficient T-ALL. ..
- Wardle D, Burgon J, Sabroe I, Bingle C, Whyte M, Renshaw S. Effective caspase inhibition blocks neutrophil apoptosis and reveals Mcl-1 as both a regulator and a target of neutrophil caspase activation. PLoS ONE. 2011;6:e15768 pubmed publisher..However, at later timepoints, declines in Mcl-1 can be reversed with effective caspase inhibition, suggesting that Mcl-1 is both an upstream regulator and a downstream target of caspase activity in human neutrophils. ..
- Cross A, Moots R, Edwards S. The dual effects of TNFalpha on neutrophil apoptosis are mediated via differential effects on expression of Mcl-1 and Bfl-1. Blood. 2008;111:878-84 pubmed
- Sieghart W, Losert D, Strommer S, Cejka D, Schmid K, Rasoul Rockenschaub S, et al. Mcl-1 overexpression in hepatocellular carcinoma: a potential target for antisense therapy. J Hepatol. 2006;44:151-7 pubmed..Mcl-1 is overexpressed in half of HCC-tissues. ASO targeting Mcl-1 revealed a prominent single agent and chemosensitizing activity against HCC in vitro. Targeting Mcl-1 might qualify as a promising novel approach in HCC therapy. ..
- Pawlikowska P, Leray I, de Laval B, Guihard S, Kumar R, Rosselli F, et al. ATM-dependent expression of IEX-1 controls nuclear accumulation of Mcl-1 and the DNA damage response. Cell Death Differ. 2010;17:1739-50 pubmed publisher..Deciphering the pathways involved in IEX-1 degradation should lead to the discovery of new therapeutic targets to increase sensitivity of tumor cells to chemotherapy. ..
- Likui W, Qun L, Wanqing Z, Haifeng S, Fangqiu L, Xiaojun L. Prognostic role of myeloid cell leukemia-1 protein (Mcl-1) expression in human gastric cancer. J Surg Oncol. 2009;100:396-400 pubmed publisher..Mcl-1 is highly upregulated in gastric cancer and high Mcl-1 expression is correlated with a poor prognosis in gastric cancer patients. Thus, Mcl-1 can be utilized as an independent prognostic factor. ..
- Kobayashi S, Lee S, Meng X, Mott J, Bronk S, Werneburg N, et al. Serine 64 phosphorylation enhances the antiapoptotic function of Mcl-1. J Biol Chem. 2007;282:18407-17 pubmed
- Shieh J, Liu K, Huang S, Chen Y, Hsieh T. Modification of alternative splicing of Mcl-1 pre-mRNA using antisense morpholino oligonucleotides induces apoptosis in basal cell carcinoma cells. J Invest Dermatol. 2009;129:2497-506 pubmed publisher..Thus, this report provides a strategy for cancer therapy in which AMOs change the alternative splicing pattern of Mcl-1 pre-mRNA and thereby induce apoptosis...
- Ewings K, Hadfield Moorhouse K, Wiggins C, Wickenden J, Balmanno K, Gilley R, et al. ERK1/2-dependent phosphorylation of BimEL promotes its rapid dissociation from Mcl-1 and Bcl-xL. EMBO J. 2007;26:2856-67 pubmed..These results provide new insights into the role of Bim in cell death and its regulation by the ERK1/2 survival pathway. ..
- Harley M, Allan L, Sanderson H, Clarke P. Phosphorylation of Mcl-1 by CDK1-cyclin B1 initiates its Cdc20-dependent destruction during mitotic arrest. EMBO J. 2010;29:2407-20 pubmed publisher..Regulation of apoptosis, therefore, is linked intrinsically to progression through mitosis and is governed by a temporal mechanism that distinguishes between normal mitosis and prolonged mitotic arrest. ..
- Ertel F, Nguyen M, Roulston A, Shore G. Programming cancer cells for high expression levels of Mcl1. EMBO Rep. 2013;14:328-36 pubmed publisher..Here, we focus on the complex strategies at play and their therapeutic implications. ..
- Sun H, Tsai A, Pan S, Ding Q, Yamaguchi H, Lin C, et al. EPOX inhibits angiogenesis by degradation of Mcl-1 through ERK inactivation. Clin Cancer Res. 2009;15:4904-14 pubmed publisher..Our results suggest that EPOX is a novel antiangiogenic agent, making it a promising lead compound for further development in the treatment of angiogenesis-related pathologies. ..
- Crawford M, Batte K, Yu L, Wu X, Nuovo G, Marsh C, et al. MicroRNA 133B targets pro-survival molecules MCL-1 and BCL2L2 in lung cancer. Biochem Biophys Res Commun. 2009;388:483-9 pubmed publisher..To our knowledge, this represents the first observation of decreased expression of miR-133B in lung cancer and that it functionally targets members of the BCL-2 family. ..
- Guoan X, Hanning W, Kaiyun C, Hao L. Adenovirus-mediated siRNA targeting Mcl-1 gene increases radiosensitivity of pancreatic carcinoma cells in vitro and in vivo. Surgery. 2010;147:553-61 pubmed publisher..Adenovirus-mediated siRNA targeting of Mcl-1 could enhance the radiosensitivity of pancreatic cancer cells both in vitro and in vivo, and thus might be a potential strategy for ameliorating cancer. ..
- De Biasio A, Vrana J, Zhou P, Qian L, Bieszczad C, Braley K, et al. N-terminal truncation of antiapoptotic MCL1, but not G2/M-induced phosphorylation, is associated with stabilization and abundant expression in tumor cells. J Biol Chem. 2007;282:23919-36 pubmed..These modifications may contribute to dysregulated MCL1 expression in cancer and represent targets for promoting its degradation to enhance tumor cell death. ..
- Zhang H, Guttikonda S, Roberts L, Uziel T, Semizarov D, Elmore S, et al. Mcl-1 is critical for survival in a subgroup of non-small-cell lung cancer cell lines. Oncogene. 2011;30:1963-8 pubmed publisher..Collectively, our results indicate that targeting Mcl-1 may improve therapy for a subset of NSCLC patients. ..
- Abulwerdi F, Liao C, Liu M, Azmi A, Aboukameel A, Mady A, et al. A novel small-molecule inhibitor of mcl-1 blocks pancreatic cancer growth in vitro and in vivo. Mol Cancer Ther. 2014;13:565-75 pubmed publisher..Collectively, these promising findings show the therapeutic potential of Mcl-1 inhibitors against pancreatic cancer and warrant further preclinical investigations. ..
- Kempkensteffen C, Hinz S, Johannsen M, Krause H, Magheli A, Christoph F, et al. Expression of Mcl-1 splicing variants in clear-cell renal cancer and their correlation with histopathological parameters and prognosis. Tumour Biol. 2009;30:73-9 pubmed publisher..004 and p = 0.011). These findings suggest Mcl-1L to provide a molecular parameter for outcome prediction in ccRCC patients, down-regulation indicating exceptionally aggressive tumour phenotypes. ..
- Thomas L, Lam C, Clark R, White M, Spiller D, Moots R, et al. Serine 162, an essential residue for the mitochondrial localization, stability and anti-apoptotic function of Mcl-1. PLoS ONE. 2012;7:e45088 pubmed..These data identify a new molecular determinant of Mcl-1 function, localization and stability that may be important for understanding the role of this protein in disease. ..
- Chipuk J, Fisher J, Dillon C, Kriwacki R, Kuwana T, Green D. Mechanism of apoptosis induction by inhibition of the anti-apoptotic BCL-2 proteins. Proc Natl Acad Sci U S A. 2008;105:20327-32 pubmed publisher..Our data show that the induction of apoptosis by inhibition of the anti-apoptotic BCL-2 repertoire requires "covert" levels of direct activators of BAX and BAK at the OMM. ..
- Hähnel P, Thaler S, Antunes E, Huber C, Theobald M, Schuler M. Targeting AKT signaling sensitizes cancer to cellular immunotherapy. Cancer Res. 2008;68:3899-906 pubmed publisher..In conclusion, cancer cell-intrinsic PKB/AKT signaling regulates the susceptibility to immune-mediated cytotoxicity. Combined targeting of signal transduction pathways may be critical for improvement of cancer immunotherapies. ..
- Wang C, Youle R. Predominant requirement of Bax for apoptosis in HCT116 cells is determined by Mcl-1's inhibitory effect on Bak. Oncogene. 2012;31:3177-89 pubmed publisher..Our data suggest that Bax and Bak are functionally redundant, but they are counteracted by distinct anti-apoptotic Bcl-2 family proteins in different species. ..
- Labisso W, Wirth M, Stojanovic N, Stauber R, Schnieke A, Schmid R, et al. MYC directs transcription of MCL1 and eIF4E genes to control sensitivity of gastric cancer cells toward HDAC inhibitors. Cell Cycle. 2012;11:1593-602 pubmed publisher..Our data reveal a new molecular mechanism for how c-MYC controls cell autonomous apoptosis and provide a rationale for a concerted inhibition of HDACs and c-MYC in gastric cancer. ..
- Dong L, Jiang C, Thorne R, Croft A, Yang F, Liu H, et al. Ets-1 mediates upregulation of Mcl-1 downstream of XBP-1 in human melanoma cells upon ER stress. Oncogene. 2011;30:3716-26 pubmed publisher..These results reveal a key mechanism by which Mcl-1 is transcriptionally upregulated in melanoma cells by ER stress, and identify Ets-1 as a potential target for inhibition to sensitize melanoma cells to apoptosis. ..
- Rutherford C, Childs S, Ohotski J, McGlynn L, Riddick M, Macfarlane S, et al. Regulation of cell survival by sphingosine-1-phosphate receptor S1P1 via reciprocal ERK-dependent suppression of Bim and PI-3-kinase/protein kinase C-mediated upregulation of Mcl-1. Cell Death Dis. 2013;4:e927 pubmed publisher..However, the functional importance of each pathway is dependent on the specific cellular context. ..
- Keuling A, Felton K, Parker A, Akbari M, Andrew S, Tron V. RNA silencing of Mcl-1 enhances ABT-737-mediated apoptosis in melanoma: role for a caspase-8-dependent pathway. PLoS ONE. 2009;4:e6651 pubmed publisher..We also report a death receptor-independent role for extrinsic pathway proteins in treatment response and suggest that caspase-8 and Bid may represent potential markers of treatment sensitivity. ..
- Luo L, Zhang T, Liu H, Lv T, Yuan D, Yao Y, et al. MiR-101 and Mcl-1 in non-small-cell lung cancer: expression profile and clinical significance. Med Oncol. 2012;29:1681-6 pubmed publisher..MiR-101 and Mcl-1 may play important roles as biomarkers for prognosis and therapeutic targets in NSCLC. ..
- Warr M, Acoca S, Liu Z, Germain M, Watson M, Blanchette M, et al. BH3-ligand regulates access of MCL-1 to its E3 ligase. FEBS Lett. 2005;579:5603-8 pubmed..This suggests that the unliganded form of Mcl-1 is sensitive to LASU1-mediated degradation of Mcl-1. ..
- Campbell S, Hazes B, Kvansakul M, Colman P, Barry M. Vaccinia virus F1L interacts with Bak using highly divergent Bcl-2 homology domains and replaces the function of Mcl-1. J Biol Chem. 2010;285:4695-708 pubmed publisher..Our data suggest that F1L replaces the antiapoptotic activity of Mcl-1 during vaccinia virus infection by interacting with Bak using highly divergent BH domains. ..
- Chu R, Terrano D, Chambers T. Cdk1/cyclin B plays a key role in mitotic arrest-induced apoptosis by phosphorylation of Mcl-1, promoting its degradation and freeing Bak from sequestration. Biochem Pharmacol. 2012;83:199-206 pubmed publisher..These results suggest that Cdk1/cyclin B plays a key role in mitotic arrest-induced apoptosis via Mcl-1 phosphorylation, promoting its degradation and subsequently releasing Bak from sequestration. ..
- Jamil S, Stoica C, Hackett T, Duronio V. MCL-1 localizes to sites of DNA damage and regulates DNA damage response. Cell Cycle. 2010;9:2843-55 pubmed..Together, these data indicate an important role for MCL-1 in coordinating DNA damage mediated checkpoint response, and have broad implications for the importance of MCL-1 in maintenance of genome integrity. ..
- Yang Yen H. Mcl-1: a highly regulated cell death and survival controller. J Biomed Sci. 2006;13:201-4 pubmed..Mcl-1 is rapidly degraded in response to cell death signals and is immediately re-induced by survival stimuli. These results indicate that Mcl-1 plays an apical role in many cell death and survival regulatory programs. ..
- Boiani M, Daniel C, Liu X, Hogarty M, Marnett L. The stress protein BAG3 stabilizes Mcl-1 protein and promotes survival of cancer cells and resistance to antagonist ABT-737. J Biol Chem. 2013;288:6980-90 pubmed publisher..These studies identify BAG3-mediated Mcl-1 stabilization as a potential target for cancer drug discovery. ..
- Germain M, Duronio V. The N terminus of the anti-apoptotic BCL-2 homologue MCL-1 regulates its localization and function. J Biol Chem. 2007;282:32233-42 pubmed..These results suggest that the N terminus of MCL-1 plays a major regulatory role, regulating coordinately the mitochondrial (anti-apoptotic) and nuclear (anti-proliferative) functions of MCL-1. ..
- Doi K, Li R, Sung S, Wu H, Liu Y, Manieri W, et al. Discovery of marinopyrrole A (maritoclax) as a selective Mcl-1 antagonist that overcomes ABT-737 resistance by binding to and targeting Mcl-1 for proteasomal degradation. J Biol Chem. 2012;287:10224-35 pubmed publisher..Taken together, these results suggest that maritoclax represents a new class of Mcl-1 inhibitors, which antagonizes Mcl-1 and overcomes ABT-737 resistance by targeting Mcl-1 for degradation. ..
- Senft D, Berking C, Graf S, Kammerbauer C, Ruzicka T, Besch R. Selective induction of cell death in melanoma cell lines through targeting of Mcl-1 and A1. PLoS ONE. 2012;7:e30821 pubmed publisher..Together, these results identify antiapoptotic proteins on which specifically melanoma cells rely on and, thus, provide a basis for the development of new Bcl-2 protein-targeting therapies. ..
- Pradelli L, Beneteau M, Chauvin C, Jacquin M, Marchetti S, Munoz Pinedo C, et al. Glycolysis inhibition sensitizes tumor cells to death receptors-induced apoptosis by AMP kinase activation leading to Mcl-1 block in translation. Oncogene. 2010;29:1641-52 pubmed publisher..In addition, this study provides a rationale for the combined use of DR ligands with AMPK activators or mTOR inhibitors in the treatment of human cancers. ..
- Masuoka H, MOTT J, Bronk S, Werneburg N, Akazawa Y, Kaufmann S, et al. Mcl-1 degradation during hepatocyte lipoapoptosis. J Biol Chem. 2009;284:30039-48 pubmed publisher..Collectively, these results implicate PKC-dependent destabilization of Mcl-1 as a mechanism contributing to hepatocyte lipoapoptosis. ..
- Longo P, Laurenti L, Gobessi S, Sica S, Leone G, Efremov D. The Akt/Mcl-1 pathway plays a prominent role in mediating antiapoptotic signals downstream of the B-cell receptor in chronic lymphocytic leukemia B cells. Blood. 2008;111:846-55 pubmed..These data demonstrate that Akt and Mcl-1 are major components of a survival pathway that can be activated in CLL B cells by antigen stimulation. ..
- Certo M, Del Gaizo Moore V, Nishino M, Wei G, Korsmeyer S, Armstrong S, et al. Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. Cancer Cell. 2006;9:351-65 pubmed..Our data allow us to distinguish a cellular state we call "primed for death," which can be determined by BH3 profiling and which correlates with dependence on antiapoptotic family members for survival. ..
- Peddaboina C, Jupiter D, Fletcher S, Yap J, Rai A, Tobin R, et al. The downregulation of Mcl-1 via USP9X inhibition sensitizes solid tumors to Bcl-xl inhibition. BMC Cancer. 2012;12:541 pubmed publisher..Mcl-1, Bcl-xL and USP9X overexpression are tumor survival mechanisms protective against chemotherapy. USP9X inhibition increases tumor cell sensitivity to various chemotherapeutic agents including Bcl-2/Bcl-xL inhibitors. ..
- Coloff J, Macintyre A, Nichols A, Liu T, Gallo C, Plas D, et al. Akt-dependent glucose metabolism promotes Mcl-1 synthesis to maintain cell survival and resistance to Bcl-2 inhibition. Cancer Res. 2011;71:5204-13 pubmed publisher..Together these data show that Mcl-1 protein synthesis is tightly controlled by metabolism and that manipulation of glucose metabolism may provide a mechanism to suppress Mcl-1 expression and sensitize cancer cells to apoptosis. ..
- Cavarretta I, Neuwirt H, Untergasser G, Moser P, Zaki M, Steiner H, et al. The antiapoptotic effect of IL-6 autocrine loop in a cellular model of advanced prostate cancer is mediated by Mcl-1. Oncogene. 2007;26:2822-32 pubmed..Our data support the concept of anti-IL-6 targeted therapy in therapy-resistant prostate cancer. ..
- Morales A, Kurtoglu M, Matulis S, Liu J, Siefker D, Gutman D, et al. Distribution of Bim determines Mcl-1 dependence or codependence with Bcl-xL/Bcl-2 in Mcl-1-expressing myeloma cells. Blood. 2011;118:1329-39 pubmed publisher..Overall, these results suggest that complex interactions, and not simply expression patterns of Bcl-2 proteins, need to be investigated to understand Bcl-2 dependence and how to better use agents, such as ABT-737. ..
- Dash R, Richards J, Su Z, Bhutia S, Azab B, Rahmani M, et al. Mechanism by which Mcl-1 regulates cancer-specific apoptosis triggered by mda-7/IL-24, an IL-10-related cytokine. Cancer Res. 2010;70:5034-45 pubmed publisher..As Mcl-1 is overexpressed in the majority of prostate cancers, mda-7/IL-24 might provide an effective therapeutic for this disease. ..
- Zhang Y, Wang H, Leng Y, Li Z, Yang Y, Xiao F, et al. Overexpression of microRNA-29b induces apoptosis of multiple myeloma cells through down regulating Mcl-1. Biochem Biophys Res Commun. 2011;414:233-9 pubmed publisher..Our results also indicated that miRNA-29b-induced apoptosis acted antagonistically with IL-6 in HMCLs. These findings suggest that miRNA-29b may play an important role in MM as a tumor suppressor. ..
- Booy E, Henson E, Gibson S. Epidermal growth factor regulates Mcl-1 expression through the MAPK-Elk-1 signalling pathway contributing to cell survival in breast cancer. Oncogene. 2011;30:2367-78 pubmed publisher..These results indicate that the EGF induced activation of Elk-1 is an important mediator of Mcl-1 expression and cell survival and therefore a potential therapeutic target in breast cancer. ..
- Alves N, Derks I, Berk E, Spijker R, van Lier R, Eldering E. The Noxa/Mcl-1 axis regulates susceptibility to apoptosis under glucose limitation in dividing T cells. Immunity. 2006;24:703-16 pubmed..We propose that the Noxa/Mcl-1 axis is an apoptosis rheostat in dividing cells, in a selective pathway that functions to restrain lymphocyte expansion and can be triggered by glucose deprivation. ..
- Gomez Bougie P, Menoret E, Juin P, Dousset C, Pellat Deceunynck C, Amiot M. Noxa controls Mule-dependent Mcl-1 ubiquitination through the regulation of the Mcl-1/USP9X interaction. Biochem Biophys Res Commun. 2011;413:460-4 pubmed publisher..The implication of Noxa in the regulation of Mcl-1 proteasomal degradation adds complexity to this process, which is governed by multiple interactions. ..
- Eckenrode E, Yang J, Velmurugan G, Foskett J, White C. Apoptosis protection by Mcl-1 and Bcl-2 modulation of inositol 1,4,5-trisphosphate receptor-dependent Ca2+ signaling. J Biol Chem. 2010;285:13678-84 pubmed publisher..Our data suggest a molecular mechanism that is shared by several anti-apoptotic Bcl-2 proteins that provides apoptosis resistance by direct interactions at the ER with the InsP(3)R that impinges on cellular Ca(2+) homeostasis. ..
- Chou C, Lee R, Yang Yen H. An internal EELD domain facilitates mitochondrial targeting of Mcl-1 via a Tom70-dependent pathway. Mol Biol Cell. 2006;17:3952-63 pubmed..Together, our results indicate that the internal EELD domain facilitates mitochondrial targeting of Mcl-1 via a Tom70-dependent pathway. ..
- Glaser S, Lee E, Trounson E, Bouillet P, Wei A, Fairlie W, et al. Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia. Genes Dev. 2012;26:120-5 pubmed publisher..Thus, targeting of Mcl-1 or regulators of its expression may be a useful strategy for the treatment of AML. ..
- Rajalingam K, Sharma M, Lohmann C, Oswald M, Thieck O, Froelich C, et al. Mcl-1 is a key regulator of apoptosis resistance in Chlamydia trachomatis-infected cells. PLoS ONE. 2008;3:e3102 pubmed publisher..Our data suggest that Mcl-1 up-regulation is primarily required to maintain apoptosis resistance in C. trachomatis-infected cells. ..
- Pepper C, Lin T, Pratt G, Hewamana S, Brennan P, Hiller L, et al. Mcl-1 expression has in vitro and in vivo significance in chronic lymphocytic leukemia and is associated with other poor prognostic markers. Blood. 2008;112:3807-17 pubmed publisher..The close correlation between Mcl-1 expression and V(H) gene mutation status, CD38 expression, and ZAP-70 expression offers a biologic explanation for their association with adverse prognosis. ..