Genomes and Genes
Gene Symbol: Mcl1
Description: myeloid cell leukemia sequence 1
Alias: AW556805, Mcl-1, induced myeloid leukemia cell differentiation protein Mcl-1 homolog, bcl-2-related protein EAT/mcl1
- Campbell K, Bath M, Turner M, Vandenberg C, Bouillet P, Metcalf D, et al. Elevated Mcl-1 perturbs lymphopoiesis, promotes transformation of hematopoietic stem/progenitor cells, and enhances drug resistance. Blood. 2010;116:3197-207 pubmed publisher..Collectively, these results demonstrate that Mcl-1 overexpression renders hematopoietic cells refractory to many cytotoxic insults, perturbs lymphopoiesis and promotes malignant transformation of hematopoietic stem and progenitor cells. ..
- Dzhagalov I, St John A, He Y. The antiapoptotic protein Mcl-1 is essential for the survival of neutrophils but not macrophages. Blood. 2007;109:1620-6 pubmed..These data suggest that Mcl-1 plays a nonredundant role in promoting the survival of neutrophils but not macrophages. ..
- Opferman J, Letai A, Beard C, Sorcinelli M, Ong C, Korsmeyer S. Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1. Nature. 2003;426:671-6 pubmed..Thus, MCL-1, which selectively inhibits the proapoptotic protein BIM, is essential both early in lymphoid development and later on in the maintenance of mature lymphocytes. ..
- Vikstrom I, Carotta S, Lüthje K, Peperzak V, Jost P, Glaser S, et al. Mcl-1 is essential for germinal center formation and B cell memory. Science. 2010;330:1095-9 pubmed publisher..We investigated the consequences of deleting genes encoding the anti-apoptotic molecules Mcl1 and Bcl2l1 (Bcl-x(L)) from B cells using an inducible system synchronized with expression of activation-induced ..
- Peperzak V, Vikstrom I, Walker J, Glaser S, Lepage M, Coquery C, et al. Mcl-1 is essential for the survival of plasma cells. Nat Immunol. 2013;14:290-7 pubmed publisher..Our results identify a critical role for Mcl-1 in the maintenance of plasma cells...
- Czabotar P, Lee E, van Delft M, Day C, Smith B, Huang D, et al. Structural insights into the degradation of Mcl-1 induced by BH3 domains. Proc Natl Acad Sci U S A. 2007;104:6217-22 pubmed..We compared the three-dimensional structures of the complexes formed between BH3 peptides of both Bim and Noxa, and we show that a discrete C-terminal sequence of the Noxa BH3 is necessary to instigate Mcl-1 degradation. ..
- Xiang Z, Luo H, Payton J, Cain J, Ley T, Opferman J, et al. Mcl1 haploinsufficiency protects mice from Myc-induced acute myeloid leukemia. J Clin Invest. 2010;120:2109-18 pubmed publisher..g., BCL2, BCL-XL, and myeloid cell leukemia 1 [MCL1]) remain poorly understood...
- Dunkle A, Dzhagalov I, He Y. Mcl-1 promotes survival of thymocytes by inhibition of Bak in a pathway separate from Bcl-2. Cell Death Differ. 2010;17:994-1002 pubmed publisher..Together, these data provide an in vivo model for Mcl-1 activity and present us with a greater understanding of the pathways that promote thymocyte survival. ..
- Ding Q, He X, Hsu J, Xia W, Chen C, Li L, et al. Degradation of Mcl-1 by beta-TrCP mediates glycogen synthase kinase 3-induced tumor suppression and chemosensitization. Mol Cell Biol. 2007;27:4006-17 pubmed..Our results indicate that the turnover of Mcl-1 by beta-TrCP is an essential mechanism for GSK-3beta-induced apoptosis and contributes to GSK-3beta-mediated tumor suppression and chemosensitization. ..
- Perciavalle R, Stewart D, Koss B, Lynch J, Milasta S, Bathina M, et al. Anti-apoptotic MCL-1 localizes to the mitochondrial matrix and couples mitochondrial fusion to respiration. Nat Cell Biol. 2012;14:575-83 pubmed publisher..Our results provide insight into how the surprisingly diverse salutary functions of MCL-1 may control the survival of both normal and cancer cells. ..
- Bradley E, Ruan M, Oursler M. Novel pro-survival functions of the Kruppel-like transcription factor Egr2 in promotion of macrophage colony-stimulating factor-mediated osteoclast survival downstream of the MEK/ERK pathway. J Biol Chem. 2008;283:8055-64 pubmed publisher..Mechanistically, Egr2 induces pro-survival Blc2 family member Mcl1 while stimulating proteasome-mediated degradation of pro-apoptotic Bim...
- Kuwana T, Bouchier Hayes L, Chipuk J, Bonzon C, Sullivan B, Green D, et al. BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly. Mol Cell. 2005;17:525-35 pubmed..In this model, the simple inhibition of antiapoptotic functions is insufficient to induce apoptosis unless a direct activator of Bax or Bak is present. ..
- Yang C, Lin N, Lee J, Huang C, Min H, Yen J, et al. Promoter knock-in mutations reveal a role of Mcl-1 in thymocyte-positive selection and tissue or cell lineage-specific regulation of Mcl-1 expression. J Immunol. 2009;182:2959-68 pubmed publisher..Together, the promoter-knock-in mouse model generated in this study not only revealed a role of Mcl-1 in thymocyte-positive selection, but also uncovered that Mcl-1 expression is regulated in a tissue or cell lineage-specific manner. ..
- Dzhagalov I, Dunkle A, He Y. The anti-apoptotic Bcl-2 family member Mcl-1 promotes T lymphocyte survival at multiple stages. J Immunol. 2008;181:521-8 pubmed..Furthermore, we demonstrate that Mcl-1 functions together with Bcl-xL to promote double-positive thymocyte survival. Thus, Mcl-1 is a critical anti-apoptotic factor for the survival of T cells at multiple stages in vivo. ..
- 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. ..
- Willis S, Fletcher J, Kaufmann T, van Delft M, Chen L, Czabotar P, et al. Apoptosis initiated when BH3 ligands engage multiple Bcl-2 homologs, not Bax or Bak. Science. 2007;315:856-9 pubmed..Our results indicate that BH3-only proteins induce apoptosis at least primarily by engaging the multiple pro-survival relatives guarding Bax and Bak. ..
- Stewart D, Koss B, Bathina M, Perciavalle R, Bisanz K, Opferman J. Ubiquitin-independent degradation of antiapoptotic MCL-1. Mol Cell Biol. 2010;30:3099-110 pubmed publisher..Supporting these findings, unmodified, in vitro-translated MCL-1 can be degraded in a cell-free system by the 20S proteasome. Taken together, these data demonstrate that MCL-1 degradation can occur independently of ubiquitinylation. ..
- Chen L, Willis S, Wei A, Smith B, Fletcher J, Hinds M, et al. Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol Cell. 2005;17:393-403 pubmed..The results suggest that apoptosis relies on selective interactions between particular subsets of these proteins and that it should be feasible to discover BH3-mimetic drugs that inactivate specific prosurvival targets. ..
- Maurer U, Charvet C, Wagman A, Dejardin E, Green D. Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1. Mol Cell. 2006;21:749-60 pubmed..The results demonstrate that the control of MCL-1 stability by GSK-3 is an important mechanism for the regulation of apoptosis by growth factors, PI3K, and AKT. ..
- 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. ..
- Pierson W, Cauwe B, Policheni A, Schlenner S, Franckaert D, Berges J, et al. Antiapoptotic Mcl-1 is critical for the survival and niche-filling capacity of Foxp3? regulatory T cells. Nat Immunol. 2013;14:959-65 pubmed publisher..Together, these data define the active processes by which Treg cells maintain homeostasis via critical survival pathways. ..
- Lin K, Lee S, Hung C, Li C, Yang Yen H, Yen J. Survival factor withdrawal-induced apoptosis of TF-1 cells involves a TRB2-Mcl-1 axis-dependent pathway. J Biol Chem. 2007;282:21962-72 pubmed..Altogether, these results suggest that the TRB2-Mcl-1 axis plays an important role in survival factor withdrawal-induced apoptosis of TF-1 cells. ..
- Huang C, Yang Yen H. The fast-mobility isoform of mouse Mcl-1 is a mitochondrial matrix-localized protein with attenuated anti-apoptotic activity. FEBS Lett. 2010;584:3323-30 pubmed publisher..This study reveals that import of Mcl-1 into the mitochondrial matrix results in the attenuation of Mcl-1's anti-apoptotic function. ..
- Li Q, Tep C, Yune T, Zhou X, Uchida T, Lu K, et al. Opposite regulation of oligodendrocyte apoptosis by JNK3 and Pin1 after spinal cord injury. J Neurosci. 2007;27:8395-404 pubmed..This report thus unveils a mechanism by which cytochrome c release is under the opposite control of JNK3 and Pin1, regulators for which the activities are intricately coupled. ..
- Lucas C, Dorward D, Tait M, Fox S, Marwick J, Allen K, et al. Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances bacterial clearance from the lung. Mucosal Immunol. 2014;7:857-68 pubmed publisher..Therefore, manipulating inflammatory cell Mcl-1 accelerates inflammation resolution without detriment to host defense against bacteria, and represents a target for treating infection-associated inflammation. ..
- Fu N, Rios A, Pal B, Soetanto R, Lun A, Liu K, et al. EGF-mediated induction of Mcl-1 at the switch to lactation is essential for alveolar cell survival. Nat Cell Biol. 2015;17:365-75 pubmed publisher..These data demonstrate that Mcl-1 is essential for mammopoiesis and identify EGF as a critical trigger of Mcl-1 translation to ensure survival of milk-producing alveolar cells. ..
- Wakatsuki S, Tokunaga S, Shibata M, Araki T. GSK3B-mediated phosphorylation of MCL1 regulates axonal autophagy to promote Wallerian degeneration. J Cell Biol. 2017;216:477-493 pubmed publisher..through activation of BECLIN1, glycogen synthase kinase 3B (GSK3B)-mediated phosphorylation of BCL2 family member MCL1 induces axonal autophagy and axonal degeneration...
- Choi Y, Harhaj E. HTLV-1 tax stabilizes MCL-1 via TRAF6-dependent K63-linked polyubiquitination to promote cell survival and transformation. PLoS Pathog. 2014;10:e1004458 pubmed publisher..Therefore, K63-linked polyubiquitination represents a novel regulatory mechanism controlling MCL-1 stability that has been usurped by a viral oncogene to precipitate cell survival and transformation. ..
- Meynet O, Zunino B, Happo L, Pradelli L, Chiche J, Jacquin M, et al. Caloric restriction modulates Mcl-1 expression and sensitizes lymphomas to BH3 mimetic in mice. Blood. 2013;122:2402-11 pubmed publisher..Exploiting this may improve the efficiency of, or prevent resistance to, cancer therapy. ..
- Magiera M, Mora S, Mojsa B, Robbins I, Lassot I, Desagher S. Trim17-mediated ubiquitination and degradation of Mcl-1 initiate apoptosis in neurons. Cell Death Differ. 2013;20:281-92 pubmed publisher..As this stabilization of Mcl-1 increased its neuroprotective effect, our data strongly suggest that Trim17-mediated ubiquitination and degradation of Mcl-1 is necessary for initiating neuronal death. ..
- Wensveen F, Slinger E, van Attekum M, Brink R, Eldering E. Antigen-affinity controls pre-germinal center B cell selection by promoting Mcl-1 induction through BAFF receptor signaling. Sci Rep. 2016;6:35673 pubmed publisher..Our findings elucidate a crucial molecular pathway of B cell selection in the earliest phases of activation by identifying a novel link between BCR affinity and BAFF-R signaling towards Mcl-1. ..
- Price A, Dai J, Bazot Q, Patel L, Nikitin P, Djavadian R, et al. Epstein-Barr virus ensures B cell survival by uniquely modulating apoptosis at early and late times after infection. elife. 2017;6: pubmed publisher..This study defines a new role for EBNA3A in the suppression of apoptosis with implications for EBV lymphomagenesis. ..
- Arbour N, Vanderluit J, Le Grand J, Jahani Asl A, Ruzhynsky V, Cheung E, et al. Mcl-1 is a key regulator of apoptosis during CNS development and after DNA damage. J Neurosci. 2008;28:6068-78 pubmed publisher..Double labeling with active caspase 3 and Tuj1 reveals that newly committed Mcl1 deficient neurons undergo apoptosis as they commence migration away from the ventricular zone...
- 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. ..
- Landeta O, Landajuela A, García Sáez A, BasaÃ±ez G. Minimalist Model Systems Reveal Similarities and Differences between Membrane Interaction Modes of MCL1 and BAK. J Biol Chem. 2015;290:17004-19 pubmed publisher..used minimalist model systems and multiple fluorescence-based techniques to examine selected membrane activities of MCL1 and BAK under apoptotic-like conditions. We show that three distinct apoptosis-related factors (i.e...
- 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. ..
- Hasan S, Sheen A, Power A, Langevin L, Xiong J, Furlong M, et al. Mcl1 regulates the terminal mitosis of neural precursor cells in the mammalian brain through p27Kip1. Development. 2013;140:3118-27 pubmed publisher..Here we show in mice that myeloid cell leukemia 1 (Mcl1), an anti-apoptotic Bcl-2 protein required for the survival of NPCs, also regulates their terminal differentiation ..
- Yip K, Kolesnikoff N, Hauschild N, Biggs L, Lopez A, Galli S, et al. The Nedd4-2/Ndfip1 axis is a negative regulator of IgE-mediated mast cell activation. Nat Commun. 2016;7:13198 pubmed publisher..Our findings reveal an important negative regulatory function for Nedd4-2 and Ndfip1 in IgE-dependent mast cell activity. ..
- Sochalska M, Tuzlak S, Egle A, Villunger A. Lessons from gain- and loss-of-function models of pro-survival Bcl2 family proteins: implications for targeted therapy. FEBS J. 2015;282:834-849 pubmed publisher..Possible limitations in clinical application may, to a certain degree, be predicted from loss-of-function phenotypes gathered from studies using gene-modified mice that we attempt to summarize and discuss in this context. ..
- Anstee N, Vandenberg C, Campbell K, Hughes P, O Reilly L, Cory S. Overexpression of Mcl-1 exacerbates lymphocyte accumulation and autoimmune kidney disease in lpr mice. Cell Death Differ. 2017;24:397-408 pubmed publisher..Comparison of the phenotype with that of other susceptible mice suggests that the development of autoimmune disease in Mcl-1tg/lpr mice may be influenced not only by Ig-producing cells but also other haemopoietic cell types. ..
- Gui J, Morales A, Maxey S, Bessette K, Ratcliffe N, Kelly J, et al. MCL1 increases primitive thymocyte viability in female mice and promotes thymic expansion into adulthood. Int Immunol. 2011;23:647-59 pubmed publisher..In the present study, a human MCL1 transgene, under the control of its endogenous promoter, resulted in enlargement of an undistorted thymus in C57/..
- Kaneko Goto T, Sato Y, Katada S, Kinameri E, Yoshihara S, Nishiyori A, et al. Goofy coordinates the acuity of olfactory signaling. J Neurosci. 2013;33:12987-96, 12996a pubmed publisher..These results demonstrate that Goofy plays an important role in establishing the acuity of olfactory sensory signaling. ..
- Akasaka T, van Lohuizen M, van der Lugt N, Mizutani Koseki Y, Kanno M, Taniguchi M, et al. Mice doubly deficient for the Polycomb Group genes Mel18 and Bmi1 reveal synergy and requirement for maintenance but not initiation of Hox gene expression. Development. 2001;128:1587-97 pubmed..Furthermore, we show an unexpected requirement for Mel18 and Bmi1 gene products to maintain stable expression of Hox cluster genes in regions caudal to the prospective anterior expression boundaries during subsequent development. ..
- Kodama T, Hikita H, Kawaguchi T, Saito Y, Tanaka S, Shigekawa M, et al. The Bcl-2 homology domain 3 (BH3)-only proteins Bim and bid are functionally active and restrained by anti-apoptotic Bcl-2 family proteins in healthy liver. J Biol Chem. 2013;288:30009-18 pubmed publisher..Hepatocyte integrity is maintained by the dynamic and well orchestrated Bcl-2 network in the healthy liver. ..
- Campbell C, Lee J, Levadoux Martin M, Wynder T, Xenocostas A, Leber B, et al. The human stem cell hierarchy is defined by a functional dependence on Mcl-1 for self-renewal capacity. Blood. 2010;116:1433-42 pubmed publisher..Our findings show that Mcl-1 is an essential regulator of stem cell self-renewal in humans and therefore represents an axis for therapeutic interventions...
- VikstrÃ¶m I, Slomp A, Carrington E, Moesbergen L, Chang C, Kelly G, et al. MCL-1 is required throughout B-cell development and its loss sensitizes specific B-cell subsets to inhibition of BCL-2 or BCL-XL. Cell Death Dis. 2016;7:e2345 pubmed publisher..Our data suggest that combination treatment targeting these pro-survival proteins could be advantageous for treatment of antibody-mediated autoimmune diseases and B-cell malignancies. ..
- De Veirman K, Van Ginderachter J, Lub S, De Beule N, Thielemans K, Bautmans I, et al. Multiple myeloma induces Mcl-1 expression and survival of myeloid-derived suppressor cells. Oncotarget. 2015;6:10532-47 pubmed..In conclusion, our data demonstrate that soluble factors from MM cells are able to generate MDSC through Mcl-1 upregulation and this cell population can be considered as a possible target in MM disease. ..
- Zhang J, D Ercole A. Expression of Mcl-1 in cerebellar granule neurons is regulated by IGF-I in a developmentally specific fashion. Brain Res Dev Brain Res. 2004;152:255-63 pubmed..These data suggest that anti-apoptotic Mcl-1 may mediate IGF-I pro-survival actions on granule neurons during the development of cerebellar cortex. They also point out pitfalls of cDNA array analyses. ..
- Colli M, Nogueira T, Allagnat F, Cunha D, Gurzov E, Cardozo A, et al. Exposure to the viral by-product dsRNA or Coxsackievirus B5 triggers pancreatic beta cell apoptosis via a Bim / Mcl-1 imbalance. PLoS Pathog. 2011;7:e1002267 pubmed publisher..These observations indicate that the balance between Mcl-1 and Bim is a key factor regulating beta cell survival during diabetogenic viral infections. ..
- Zhang Z, Song T, Zhang T, Gao J, Wu G, An L, et al. A novel BH3 mimetic S1 potently induces Bax/Bak-dependent apoptosis by targeting both Bcl-2 and Mcl-1. Int J Cancer. 2011;128:1724-35 pubmed publisher..S1 represents a novel chemical class of antitumor leads that function solely as BH3 mimetics and pan-Bcl-2 inhibitors. In the meanwhile, S1 could become a unique tool for interactions between Bcl-2 family proteins. ..
- Inoue S, Browne G, Melino G, Cohen G. Ordering of caspases in cells undergoing apoptosis by the intrinsic pathway. Cell Death Differ. 2009;16:1053-61 pubmed publisher..The processing of caspase-2 and -6 occurs within the cytoplasm and active caspase-6 is then responsible for both the processing of caspase-8 and the cleavage of caspase-6 substrates, including lamin A/C. ..
- Mills J, Malina A, Pelletier J. Inhibiting mitochondrial-dependent proteolysis of Mcl-1 promotes resistance to DNA damage. Cell Cycle. 2012;11:88-98 pubmed publisher..Our data uncover an important relationship between the mitochondria and the Mcl-1 N terminus in dictating cell fate following DNA damage. ..
- Fernández Marrero Y, Spinner S, Kaufmann T, Jost P. Survival control of malignant lymphocytes by anti-apoptotic MCL-1. Leukemia. 2016;30:2152-2159 pubmed publisher..This review summarizes the role of MCL-1 in B- and T-cell lymphoma and discusses its potential as a therapeutic target. ..
- Kodama Y, Taura K, Miura K, Schnabl B, Osawa Y, Brenner D. Antiapoptotic effect of c-Jun N-terminal Kinase-1 through Mcl-1 stabilization in TNF-induced hepatocyte apoptosis. Gastroenterology. 2009;136:1423-34 pubmed publisher..jnk2-/- Hepatocytes are resistant to TNF-induced apoptosis. Activated JNK1 contributes to this antiapoptotic phenotype of jnk2-/- hepatocytes through phosphorylation-mediated stabilization of Mcl-1. ..
- Morel C, Carlson S, White F, Davis R. Mcl-1 integrates the opposing actions of signaling pathways that mediate survival and apoptosis. Mol Cell Biol. 2009;29:3845-52 pubmed publisher..Together, these data establish that Mcl-1 functions as a site of signal integration between the proapoptotic activity of JNK and the prosurvival activity of the AKT pathway that inhibits GSK3. ..
- Weber A, Boger R, Vick B, Urbanik T, Haybaeck J, Zoller S, et al. Hepatocyte-specific deletion of the antiapoptotic protein myeloid cell leukemia-1 triggers proliferation and hepatocarcinogenesis in mice. Hepatology. 2010;51:1226-36 pubmed publisher..Our findings might have implications for understanding apoptosis-related human liver diseases. ..
- Mori M, Burgess D, Gefrides L, Foreman P, Opferman J, Korsmeyer S, et al. Expression of apoptosis inhibitor protein Mcl1 linked to neuroprotection in CNS neurons. Cell Death Differ. 2004;11:1223-33 pubmedb>Mcl1 is a Bcl2-related antiapoptotic protein originally isolated from human myeloid leukemia cells. Unlike Bcl2, expression has not been reported in CNS neurons...
- Woods N, Yamaguchi H, Lee F, Bhalla K, Wang H. Anoikis, initiated by Mcl-1 degradation and Bim induction, is deregulated during oncogenesis. Cancer Res. 2007;67:10744-52 pubmed..Therefore, Mcl-1 degradation primes the cell for Bax activation and anoikis, which can be blocked by oncogenic signaling in metastatic cells. ..
- Shinohara M, Ybanez M, Win S, Than T, Jain S, Gaarde W, et al. Silencing glycogen synthase kinase-3beta inhibits acetaminophen hepatotoxicity and attenuates JNK activation and loss of glutamate cysteine ligase and myeloid cell leukemia sequence 1. J Biol Chem. 2010;285:8244-55 pubmed publisher..Taken together our results suggest that activation of GSK-3beta is a key mediator of the initial phase of APAP-induced liver injury through modulating GCL and Mcl-1 degradation, as well as JNK activation in liver. ..
- Spinner S, Crispatzu G, Yi J, Munkhbaatar E, Mayer P, Höckendorf U, et al. Re-activation of mitochondrial apoptosis inhibits T-cell lymphoma survival and treatment resistance. Leukemia. 2016;30:1520-30 pubmed publisher..We conclude that re-activation of mitochondrial apoptosis by blockade of MCL-1 represents a promising therapeutic strategy to treat T-cell lymphoma. ..
- Day C, Chen L, Richardson S, Harrison P, Huang D, Hinds M. Solution structure of prosurvival Mcl-1 and characterization of its binding by proapoptotic BH3-only ligands. J Biol Chem. 2005;280:4738-44 pubmed..Elucidating the selective action of certain BH3-only ligands is required for delineating their mode of action and will aid the search for effective BH3-mimetic drugs. ..
- Vick B, Weber A, Urbanik T, Maass T, Teufel A, Krammer P, et al. Knockout of myeloid cell leukemia-1 induces liver damage and increases apoptosis susceptibility of murine hepatocytes. Hepatology. 2009;49:627-36 pubmed publisher..The present study provides in vivo evidence that Mcl-1 is a crucial antiapoptotic factor for the liver, contributing to hepatocellular homeostasis and protecting hepatocytes from apoptosis induction. ..
- Kubota Y, Kinoshita K, Suetomi K, Fujimori A, Takahashi S. Mcl-1 depletion in apoptosis elicited by ionizing radiation in peritoneal resident macrophages of C3H mice. J Immunol. 2007;178:2923-31 pubmed..It was concluded that the apoptosis elicited in C3H mouse PRM by ionizing radiation was attributable to the depletion of Mcl-1 through radiation-induced arrest of global protein synthesis. ..
- Omari S, Waters M, Naranian T, Kim K, Perumalsamy A, Chi M, et al. Mcl-1 is a key regulator of the ovarian reserve. Cell Death Dis. 2015;6:e1755 pubmed publisher..We thus recognize MCL-1 as the essential survival factor required for conservation of the postnatal PMF pool, growing follicle survival and effective oocyte mitochondrial function. ..
- Ho C, Chhabra A, Starkl P, Schnorr P, Wilmes S, Moraga I, et al. Decoupling the Functional Pleiotropy of Stem Cell Factor by Tuning c-Kit Signaling. Cell. 2017;168:1041-1052.e18 pubmed publisher..The approach of biasing cell activation by tuning signaling thresholds and outputs has applications to many dimeric receptor-ligand systems. ..
- Day C, Smits C, Fan F, Lee E, Fairlie W, Hinds M. Structure of the BH3 domains from the p53-inducible BH3-only proteins Noxa and Puma in complex with Mcl-1. J Mol Biol. 2008;380:958-71 pubmed publisher..Our studies show that unstructured peptides, such as the BH3 domains, behave like their structured counterparts and can bind tightly and selectively in an enthalpically driven process. ..
- Wang J, Lai M, Yang Yen H. Interleukin-3 stimulation of mcl-1 gene transcription involves activation of the PU.1 transcription factor through a p38 mitogen-activated protein kinase-dependent pathway. Mol Cell Biol. 2003;23:1896-909 pubmed..Taken together, our results demonstrate that IL-3 stimulation of mcl-1 gene transcription through the SIE motif involves phosphorylation of PU.1 at serine 142 by a p38(MAPK)-dependent pathway. ..
- Wang F, Wang X, Wang C, Wang X, Zhang Y, Wu J, et al. Suppression of Mcl-1 induces apoptosis in mouse peritoneal macrophages infected with Mycobacterium tuberculosis. Microbiol Immunol. 2016;60:215-27 pubmed publisher..Taken together, these results suggest that specific downregulation of Mcl-1 significantly increases apoptosis of peritoneal macrophages and that the MAPK signaling pathway is the primary mediator of Mcl-1 expression. ..
- Woo S, Min K, Seo B, Nam J, Choi K, Yoo Y, et al. Cafestol overcomes ABT-737 resistance in Mcl-1-overexpressed renal carcinoma Caki cells through downregulation of Mcl-1 expression and upregulation of Bim expression. Cell Death Dis. 2014;5:e1514 pubmed publisher..Taken together, cafestol may be effectively used to enhance ABT-737 sensitivity in cancer therapy via downregulation of Mcl-1 expression and upregulation of Bim expression. ..
- Carrington E, Zhang J, Sutherland R, Vikstrom I, Brady J, Soo P, et al. Prosurvival Bcl-2 family members reveal a distinct apoptotic identity between conventional and plasmacytoid dendritic cells. Proc Natl Acad Sci U S A. 2015;112:4044-9 pubmed publisher..The molecular basis of survival of different DC subsets thus advocates the antagonism of selective BCL-2 family members for treating diseases pertaining to distinct DC subsets. ..
- Chen S, Dai Y, Harada H, Dent P, Grant S. Mcl-1 down-regulation potentiates ABT-737 lethality by cooperatively inducing Bak activation and Bax translocation. Cancer Res. 2007;67:782-91 pubmed..These findings provide a mechanistic basis for simultaneously targeting Mcl-1 and Bcl-2/Bcl-xL in leukemia. ..
- Jain R, Sheridan J, Policheni A, Heinlein M, Gandolfo L, Dewson G, et al. A critical epithelial survival axis regulated by MCL-1 maintains thymic function in mice. Blood. 2017;130:2504-2515 pubmed publisher..This signaling axis governing TEC survival and thymic function represents a new target for strategies for thymic protection and regeneration. ..