myeloid cell leukemia sequence 1 protein


Summary: A member of the myeloid leukemia factor (MLF) protein family with multiple alternatively spliced transcript variants encoding different protein isoforms. In hematopoietic cells, it is located mainly in the nucleus, and in non-hematopoietic cells, primarily in the cytoplasm with a punctate nuclear localization. MLF1 plays a role in cell cycle differentiation.

Top Publications

  1. Tai X. MCL-1 keeps a charming home for thymocytes. Blood. 2017;130:2448-2450 pubmed publisher
  2. Nijhuis A, Curciarello R, Mehta S, Feakins R, Bishop C, Lindsay J, et al. MCL-1 is modulated in Crohn's disease fibrosis by miR-29b via IL-6 and IL-8. Cell Tissue Res. 2017;368:325-335 pubmed publisher
    ..We propose that an anti-fibrotic miR-29b/IL-6 IL-8/MCL-1L axis may influence intestinal fibrosis in CD. In the future, therapeutic modulation of this pathway might contribute to the management of fibrosis in CD. ..
  3. Wu W, Yang Y, Deng G, Ma L, Wei G, Zheng G, et al. Vernodalol enhances TRAIL-induced apoptosis in diffuse large B-cell lymphoma cells. Mol Carcinog. 2017;56:2190-2199 pubmed publisher
    ..Therefore, combining TRAIL with vernodalol, a naturally occurring agent, may represent a promising therapeutic approach for DLBCL. ..
  4. Ruefli Brasse A, Reed J. Therapeutics targeting Bcl-2 in hematological malignancies. Biochem J. 2017;474:3643-3657 pubmed publisher
    ..Here, we review recent progress in direct and selective targeting of Bcl-2 family proteins for cancer therapy and the search for rationale combinations...
  5. Gregory G, Hogg S, Kats L, Vidacs E, Baker A, Gilan O, et al. CDK9 inhibition by dinaciclib potently suppresses Mcl-1 to induce durable apoptotic responses in aggressive MYC-driven B-cell lymphoma in vivo. Leukemia. 2015;29:1437-41 pubmed publisher
  6. Katoh N, Kraft S, Wessendorf J, Bieber T. The high-affinity IgE receptor (FcepsilonRI) blocks apoptosis in normal human monocytes. J Clin Invest. 2000;105:183-90 pubmed
    ..This process may contribute to the establishment of chronic allergic disorders such as atopic dermatitis. ..
  7. Klann J, Remedios K, Kim S, Metz P, Lopez J, Mack L, et al. Talin Plays a Critical Role in the Maintenance of the Regulatory T Cell Pool. J Immunol. 2017;198:4639-4651 pubmed publisher
    ..Collectively, our data suggest a critical role for talin in Treg cell-mediated maintenance of immune homeostasis. ..
  8. Millman S, Pagano M. MCL1 meets its end during mitotic arrest. EMBO Rep. 2011;12:384-5 pubmed publisher
  9. Shiomi Y, Yoshimura M, Kuki K, Hori Y, Tanaka T. Z-360 Suppresses Tumor Growth in MIA PaCa-2-bearing Mice via Inhibition of Gastrin-induced Anti-Apoptotic Effects. Anticancer Res. 2017;37:4127-4137 pubmed
    ..These results suggest that Z-360 exerts an anti-tumor effect through a reduction in anti-apoptosis factors by blocking CCK2R. ..

More Information


  1. Xu G, Liu T, Zhou Y, Yang X, Fang H. 1-Phenyl-1H-indole derivatives as a new class of Bcl-2/Mcl-1 dual inhibitors: Design, synthesis, and preliminary biological evaluation. Bioorg Med Chem. 2017;25:5548-5556 pubmed publisher
    ..sub> Furthermore, Compound 9c and 9h showed better anti-proliferative activity than WL-276. ..
  2. Sun S. N-acetylcysteine, reactive oxygen species and beyond. Cancer Biol Ther. 2010;9:109-10 pubmed
  3. Ma B, Yuan Z, Zhang L, Lv P, Yang T, Gao J, et al. Long non-coding RNA AC023115.3 suppresses chemoresistance of glioblastoma by reducing autophagy. Biochim Biophys Acta Mol Cell Res. 2017;1864:1393-1404 pubmed publisher
    ..Thus, these data indicate that the AC023115.3-miR-26a-GSK3? signalling axis plays an important role in reducing the chemoresistance of glioma. ..
  4. Qu N, Hu J, Liu L, Zhang T, Sun G, Shi R, et al. SIRT6 is upregulated and associated with cancer aggressiveness in papillary thyroid cancer via BRAF/ERK/Mcl?1 pathway. Int J Oncol. 2017;50:1683-1692 pubmed publisher
    ..In conclusion, these results suggest that SIRT6 enhances cell aggressiveness in PTC via BRAF/ERK/Mcl?1 pathway, and thus may be a promising target in the treatment of the disease. ..
  5. Lee J, Shin E, Kim B, Kim B, Chitsazian Yazdi M, Iranshahi M, et al. Auraptene Induces Apoptosis via Myeloid Cell Leukemia 1-Mediated Activation of Caspases in PC3 and DU145 Prostate Cancer Cells. Phytother Res. 2017;31:891-898 pubmed publisher
    ..Copyright © 2017 John Wiley & Sons, Ltd. ..
  6. Li N, Yuan Q, Cao X, Zhang Y, Min Z, Xu S, et al. Opposite effects of HDAC5 and p300 on MRTF-A-related neuronal apoptosis during ischemia/reperfusion injury in rats. Cell Death Dis. 2017;8:e2624 pubmed publisher
    ..The results suggest that both HDAC5 and p300 are involved in MRTF-A-mediated effect on neuronal apoptosis during ischemia/reperfusion injury, but with opposite effects. ..
  7. Boege Y, Malehmir M, Healy M, Bettermann K, Lorentzen A, Vucur M, et al. A Dual Role of Caspase-8 in Triggering and Sensing Proliferation-Associated DNA Damage, a Key Determinant of Liver Cancer Development. Cancer Cell. 2017;32:342-359.e10 pubmed publisher
    ..It may represent a DNA damage-sensing mechanism in hepatocytes that can act via JNK and subsequent phosphorylation of the histone variant H2AX. ..
  8. Wu X, Zhang L, Toombs J, Kuo Y, Piazza J, Tuladhar R, et al. Extra-mitochondrial prosurvival BCL-2 proteins regulate gene transcription by inhibiting the SUFU tumour suppressor. Nat Cell Biol. 2017;19:1226-1236 pubmed publisher
    ..Our findings delineate a chemical strategy for countering drug resistance in GLI-associated tumours and reveal unanticipated functions for BCL-2 proteins as transcriptional regulators. ..
  9. Cazanave S, Gores G. The liver's dance with death: two Bcl-2 guardian proteins from the abyss. Hepatology. 2009;50:1009-13 pubmed publisher
  10. Besbes S, Billard C. First MCL-1-selective BH3 mimetics as potential therapeutics for targeted treatment of cancer. Cell Death Dis. 2015;6:e1810 pubmed publisher
  11. Meynet O, Beneteau M, Jacquin M, Pradelli L, Cornille A, Carles M, et al. Glycolysis inhibition targets Mcl-1 to restore sensitivity of lymphoma cells to ABT-737-induced apoptosis. Leukemia. 2012;26:1145-7 pubmed publisher
  12. Yuan B, Chapman J, Ding M, Wang J, Jiang B, Rojanasakul Y, et al. TRAIL and proteasome inhibitors combination induces a robust apoptosis in human malignant pleural mesothelioma cells through Mcl-1 and Akt protein cleavages. BMC Cancer. 2013;13:140 pubmed publisher
    ..The combinatorial treatment using TRAIL and PI may represent an effective new treatment for MPMs. ..
  13. Xia H, Cui H, Su L, Zhang Z, Yang X, Ning S, et al. Clinical significance and expression of PUMA, MCL-1, and p53 in human renal cell carcinoma and para-carcinoma tissues. Genet Mol Res. 2017;16: pubmed publisher
    ..05).The expression of PUMA, MCL-1, and p53 can reflect the biological behavior of renal cell carcinoma, and can be used to indicate tumor invasion, progression, and prognosis. ..
  14. Zhang Y, Shi C, Yin L, Zhou W, Wang H, Seng J, et al. Inhibition of Mcl-1 enhances Pevonedistat-triggered apoptosis in osteosarcoma cells. Exp Cell Res. 2017;358:234-241 pubmed publisher
    ..Altogether, our study shows that Mcl-1 is a critical resistance factor to Pevonedistat monotherapy, and suggests that Pevonedistat in combinations with flavopiridol may achieve better anticancer therapy. ..
  15. Ye M, Zhang Y, Zhang X, Zhang J, Jing P, Cao L, et al. Targeting FBW7 as a Strategy to Overcome Resistance to Targeted Therapy in Non-Small Cell Lung Cancer. Cancer Res. 2017;77:3527-3539 pubmed publisher
    ..i>Cancer Res; 77(13); 3527-39. ©2017 AACR. ..
  16. Okumu D, East M, Levine M, Herring L, Zhang R, Gilbert T, et al. BIRC6 mediates imatinib resistance independently of Mcl-1. PLoS ONE. 2017;12:e0177871 pubmed publisher
    ..Hence, BIRC6 may be a novel target for the treatment of drug-resistant CML where Mcl-1 or CDK9 inhibitors have failed. ..
  17. Kang M, Yun H, Lee J. KRIBB11 accelerates Mcl-1 degradation through an HSF1-independent, Mule-dependent pathway in A549 non-small cell lung cancer cells. Biochem Biophys Res Commun. 2017;492:304-309 pubmed publisher
    ..Taken together, our results suggest that targeting Mcl-1 with KRIBB11 treatment, while simultaneously downregulating BIS, could be a therapeutic strategy in NSCLC. ..
  18. Frieler R, Chung Y, Ahlers C, Gheordunescu G, Song J, Vigil T, et al. Genetic neutrophil deficiency ameliorates cerebral ischemia-reperfusion injury. Exp Neurol. 2017;298:104-111 pubmed publisher
  19. Basu A, Sridharan S. Regulation of anti-apoptotic Bcl-2 family protein Mcl-1 by S6 kinase 2. PLoS ONE. 2017;12:e0173854 pubmed publisher
    ..JNK1 knockdown also had a modest effect in attenuating the increase in doxorubicin-induced apoptosis caused by S6K2 deficiency. These results suggest that S6K2 regulates apoptosis via multiple mechanisms, and involves both Akt and JNK. ..
  20. Tong J, Wang P, Tan S, Chen D, Nikolovska Coleska Z, Zou F, et al. Mcl-1 Degradation Is Required for Targeted Therapeutics to Eradicate Colon Cancer Cells. Cancer Res. 2017;77:2512-2521 pubmed publisher
    ..i>Cancer Res; 77(9); 2512-21. ©2017 AACR. ..
  21. Zeng J, Li S, Wu X, Liu D, Wan X. [Study on impact of ethanol extracts from Sedum sarmentosum in inhibiting STAT-3 signaling and inducing apoptosis of human hepatocellular carcinoma cell line HepG2]. Zhongguo Zhong Yao Za Zhi. 2014;39:3349-52 pubmed
    ..ESB inhibits HepG2 cell proliferation and induces apoptosis by inhibiting STAT-3 signaling and Mcl-1 and Bcl-2 expressions. ..
  22. Séry Q, Rabé M, Oliver L, Vallette F, Gratas C. HB-EGF is associated with DNA damage and Mcl-1 turnover in human glioma cell lines treated by Temozolomide. Biochem Biophys Res Commun. 2017;493:1377-1383 pubmed publisher
    ..Our data demonstrate a new role for HB-EGF in TMZ treated cell lines...
  23. Ebner F, Sedlyarov V, Tasciyan S, Ivin M, Kratochvill F, Gratz N, et al. The RNA-binding protein tristetraprolin schedules apoptosis of pathogen-engaged neutrophils during bacterial infection. J Clin Invest. 2017;127:2051-2065 pubmed publisher
    ..Our study demonstrates that posttranscriptional gene regulation by TTP schedules the termination of the antimicrobial engagement of neutrophils. The balancing role of TTP comes at the cost of an increased risk of bacterial infections. ..
  24. Kang X, Zhang J, Zhang Q, Cui Y, Wang Y, Kou W, et al. Degradation of Mcl-1 through GSK-3? Activation Regulates Apoptosis Induced by Bufalin in Non-Small Cell Lung Cancer H1975 Cells. Cell Physiol Biochem. 2017;41:2067-2076 pubmed publisher
    ..Bufalin induced cell apoptosis in H1975 cells may be through downregulation of Mcl-1. Proteasomal degradation of Mcl-1 via GSK-3? activation was involved in bufalin-induced apoptosis. ..
  25. Anasir M, Caria S, Skinner M, Kvansakul M. Structural basis of apoptosis inhibition by the fowlpox virus protein FPV039. J Biol Chem. 2017;292:9010-9021 pubmed publisher
    ..This work therefore provides a mechanistic platform to better understand FPV039-mediated apoptosis inhibition. ..
  26. Mosaad S, Zaitone S, Ibrahim A, El Baz A, Abo Elmatty D, Moustafa Y. Celecoxib aggravates cardiac apoptosis in L-NAME-induced pressure overload model in rats: Immunohistochemical determination of cardiac caspase-3, Mcl-1, Bax and Bcl-2. Chem Biol Interact. 2017;272:92-106 pubmed publisher
    ..The work results shed the light on the putative pro-apoptotic effect of celecoxib at a risk state of pressure overload comparable to the clinical condition of essential hypertension. ..
  27. Singh P, Roukounakis A, Frank D, Kirschnek S, Das K, Neumann S, et al. Dynein light chain 1 induces assembly of large Bim complexes on mitochondria that stabilize Mcl-1 and regulate apoptosis. Genes Dev. 2017;31:1754-1769 pubmed publisher
  28. Zhao C, Wang Y, Jin H, Yu T. Knockdown of microRNA-203 alleviates LPS-induced injury by targeting MCL-1 in C28/I2 chondrocytes. Exp Cell Res. 2017;359:171-178 pubmed publisher
    ..In conclusion, this study suggests that miR-203 suppression may inhibit the progression of OA by targeting MCL-1 and activating the Wnt/?-Catenin and JAK/STAT signal pathways. ..
  29. Meyerovich K, Violato N, Fukaya M, Dirix V, Pachera N, Marselli L, et al. MCL-1 Is a Key Antiapoptotic Protein in Human and Rodent Pancreatic ?-Cells. Diabetes. 2017;66:2446-2458 pubmed publisher
    ..Development of strategies to prevent MCL-1 loss in the early stages of T1D may enhance ?-cell survival and thereby delay or prevent disease progression. ..
  30. Seo S, Cho H, Min K, Woo S, Kim S, Park J, et al. Thioridazine enhances sensitivity to carboplatin in human head and neck cancer cells through downregulation of c-FLIP and Mcl-1 expression. Cell Death Dis. 2017;8:e2599 pubmed publisher
    ..hy926). Collectively, our study demonstrates that combined treatment with carboplatin and thioridazine induces apoptosis through proteasomal degradation of Mcl-1 and c-FLIP by upregulation of Nrf2-dependent PSMA5 expression. ..
  31. Faber A, WONG K, Engelman J. Differences underlying EGFR and HER2 oncogene addiction. Cell Cycle. 2010;9:851-2 pubmed
  32. Bhat U, Gartel A. Nucleoside analog ARC targets Mcl-1 to induce apoptosis in leukemia cells. Leukemia. 2010;24:851-5 pubmed publisher
  33. Yu H, Zhang X, Liu R, Li H, Xiao X, Zhou Y, et al. Mcl-1 suppresses abasic site repair following bile acid-induced hepatic cellular DNA damage. Tumour Biol. 2017;39:1010428317712102 pubmed publisher
    ..These results potentially explain how bile acid accumulation results in genetic instability and carcinogenesis. ..
  34. Radhakrishnan H, Ilm K, Walther W, Shirasawa S, Sasazuki T, Daniel P, et al. MACC1 regulates Fas mediated apoptosis through STAT1/3 - Mcl-1 signaling in solid cancers. Cancer Lett. 2017;403:231-245 pubmed publisher
    ..Altogether, we reveal a novel death receptor-mediated apoptosis regulatory mechanism by MACC1 in solid cancers through modulation of the STAT1/3-Mcl-1 axis. ..
  35. Venkata J, An N, Stuart R, Costa L, Cai H, Coker W, et al. Inhibition of sphingosine kinase 2 downregulates the expression of c-Myc and Mcl-1 and induces apoptosis in multiple myeloma. Blood. 2014;124:1915-25 pubmed
    ..Our data demonstrated that SK2 provides a novel therapeutic target for the treatment of MM.This trial was registered at as #NCT01410981. ..
  36. Jun D, Kim H, Jang W, Lee J, Fukui K, Kim Y. Ectopic overexpression of LAPTM5 results in lysosomal targeting and induces Mcl-1 down-regulation, Bak activation, and mitochondria-dependent apoptosis in human HeLa cells. PLoS ONE. 2017;12:e0176544 pubmed publisher
  37. Xie Q, Wang S, Zhao Y, Zhang Z, Qin C, Yang X. MiR-519d impedes cisplatin-resistance in breast cancer stem cells by down-regulating the expression of MCL-1. Oncotarget. 2017;8:22003-22013 pubmed publisher
    ..Taken together, the present study suggests that miR-519d reduces chemoresistance in breast cancer stem cells, and understanding of miR-519d may be helpful for increasing the efficacy of chemotherapy. ..
  38. Ah Cann C, Tailler M, Kueh A, Herold M, Opferman J, Asselin Labat M, et al. Male sterility in Mcl-1-flox mice is not due to enhanced Mcl1 protein stability. Cell Death Dis. 2016;7:e2490 pubmed publisher
  39. Arechaga Ocampo E, López Camarillo C, Villegas Sepúlveda N, González De la Rosa C, Perez Añorve I, Roldan Perez R, et al. Tumor suppressor miR-29c regulates radioresistance in lung cancer cells. Tumour Biol. 2017;39:1010428317695010 pubmed publisher
    ..Together, these results indicate a new role of miR-29c in radioresistance, highlighting their potential as a novel biomarker for outcomes of radiotherapy in lung cancer. ..
  40. Zhao B, Sensintaffar J, Bian Z, Belmar J, Lee T, Olejniczak E, et al. Structure of a Myeloid cell leukemia-1 (Mcl-1) inhibitor bound to drug site 3 of Human Serum Albumin. Bioorg Med Chem. 2017;25:3087-3092 pubmed publisher
    ..Structural studies of molecules that bind to this third site may provide insight into how some higher molecular weight compounds bind to albumin and could be used to aid in the design of compounds with reduced albumin binding. ..
  41. Zhao X, Kong F, Wang L, Zhang H. c-FLIP and the NOXA/Mcl-1 axis participate in the synergistic effect of pemetrexed plus cisplatin in human choroidal melanoma cells. PLoS ONE. 2017;12:e0184135 pubmed publisher
    ..Our study provides important mechanistic insights into potential cancer treatment with pemetrexed plus cisplatin and enriches our understanding of human choroidal melanoma. ..
  42. Fan Y, Arechederra M, Richelme S, Daian F, Novello C, Calderaro J, et al. A phosphokinome-based screen uncovers new drug synergies for cancer driven by liver-specific gain of nononcogenic receptor tyrosine kinases. Hepatology. 2017;66:1644-1661 pubmed publisher
    ..Hepatology 2017;66:1644-1661). ..
  43. Nishida Y, Maeda A, Kim M, Cao L, Kubota Y, Ishizawa J, et al. The novel BMI-1 inhibitor PTC596 downregulates MCL-1 and induces p53-independent mitochondrial apoptosis in acute myeloid leukemia progenitor cells. Blood Cancer J. 2017;7:e527 pubmed publisher
  44. Powell C. Rounding up apoptosis resistance targets in lung cancer. Am J Respir Cell Mol Biol. 2009;41:7-8 pubmed publisher