Affinage

MCL1

Induced myeloid leukemia cell differentiation protein Mcl-1 · UniProt Q07820

Round 2 corrected
Length
350 aa
Mass
37.3 kDa
Annotated
2026-04-28
130 papers in source corpus 45 papers cited in narrative 45 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MCL-1 is an anti-apoptotic BCL-2 family protein that guards mitochondrial outer membrane integrity by sequestering the pro-apoptotic effectors BAK and BAX and the BH3-only activators BIM and BID through its BH3-binding groove, thereby preventing cytochrome c release and caspase activation (PMID:15901672, PMID:15694340, PMID:16697956). Its abundance is tightly controlled by rapid proteasomal turnover orchestrated by multiple E3 ubiquitin ligases—Mule/ARF-BP1, SCF(FBW7), Trim17, APC/C—and counterbalanced by deubiquitinases USP9X, USP13, and Ku70, with GSK-3β phosphorylation of S159 serving as a central degradation trigger (PMID:15989957, PMID:21368833, PMID:22976837, PMID:20023629, PMID:16543145, PMID:29987118); MCL-1 can also be degraded ubiquitin-independently by the 20S proteasome (PMID:20385764). Beyond apoptosis suppression, a mitochondrial matrix-localized form of MCL-1 sustains mitochondrial morphology, oxidative phosphorylation, and selective mitophagy independently of its anti-apoptotic role, and a nuclear pool inhibits Ku-dependent non-homologous end joining to favor homologous recombination repair (PMID:23026029, PMID:23788622, PMID:28978427, PMID:29227281, PMID:35563775). MCL-1 is essential for survival of neutrophils, early definitive erythroid progenitors, and cardiomyocytes, and its genetic ablation causes neutropenia, embryonic anemia, and lethal cardiomyopathy, respectively (PMID:19064728, PMID:33512417, PMID:23788622).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1993 High

    Identification of MCL1 as an immediate-early gene induced during myeloid differentiation with BCL-2 sequence homology established it as a new anti-apoptotic family member, opening the question of its specific survival functions.

    Evidence cDNA cloning and Northern blot from phorbol-ester-treated ML-1 cells

    PMID:7682708

    Open questions at the time
    • No biochemical function or binding partners yet identified
    • Expression pattern in non-myeloid lineages unknown
  2. 2002 High

    Antisense knockdown demonstrated that MCL-1, rather than BCL-2 or BCL-XL, is the dominant survival factor in multiple myeloma, motivating mechanistic dissection of its mitochondrial role.

    Evidence Antisense oligonucleotides against MCL-1 in myeloma cell lines and primary samples with apoptosis readouts

    PMID:12070027

    Open questions at the time
    • Direct protein–protein interactions at mitochondria not yet mapped
    • Mechanism of MCL-1 specificity over BCL-2 unknown
  3. 2003 High

    UV-induced rapid proteasomal destruction of MCL-1 was shown to be a required upstream event for cytochrome c release, establishing that MCL-1 turnover is a gatekeeping step in stress-induced apoptosis.

    Evidence Proteasome inhibitor rescue, subcellular fractionation, and genetic epistasis in UV-treated cells

    PMID:12783855

    Open questions at the time
    • Identity of E3 ligase(s) mediating UV-triggered MCL-1 degradation unknown
    • Whether degradation is ubiquitin-dependent not tested
  4. 2005 High

    A suite of studies defined MCL-1's interaction specificity: BAK is sequestered by MCL-1 and BCL-XL but not other family members, Noxa selectively binds MCL-1 while Bad binds BCL-2/BCL-XL, and BH3-only proteins function as either direct BAX activators or MCL-1 derepressors, establishing the 'selective engagement' model of apoptotic signaling.

    Evidence Fluorescence polarization binding assays, reciprocal Co-IP, cell-free reconstituted membrane permeabilization, genetic epistasis

    PMID:15694340 PMID:15721256 PMID:15901672

    Open questions at the time
    • Structural basis for selectivity not yet resolved at atomic level
    • In vivo hierarchy of BH3-only proteins at MCL-1 not tested
  5. 2005 High

    Mule/ARF-BP1 was identified as the first MCL-1-specific E3 ubiquitin ligase, using a BH3-like domain to bind MCL-1 and polyubiquitinate it for DNA-damage-induced degradation, revealing how apoptotic competence is acquired through targeted MCL-1 proteolysis.

    Evidence Biochemical purification, in vitro ubiquitination reconstitution, RNAi epistasis

    PMID:15989957

    Open questions at the time
    • Relative contribution of Mule versus other E3 ligases in different tissues unknown
    • Lysine acceptor site preference not fully mapped
  6. 2005 High

    TCTP was found to stabilize MCL-1 by blocking ubiquitin-dependent degradation, revealing that MCL-1 levels are set by the balance between stabilizing and destabilizing factors.

    Evidence Co-IP, mutagenesis (K257V), cycloheximide chase, RNAi in multiple cell types

    PMID:15798198

    Open questions at the time
    • Mechanism by which TCTP blocks ubiquitination not elucidated
    • Physiological contexts where TCTP–MCL-1 axis is rate-limiting unclear
  7. 2006 High

    GSK-3β was established as the kinase that phosphorylates MCL-1 at S159 to trigger ubiquitin-dependent degradation, with AKT blocking this via GSK-3β inactivation, providing a direct link between growth-factor signaling and MCL-1 abundance.

    Evidence In vitro kinase assay, S159A mutagenesis, pharmacological inhibitors, cycloheximide chase

    PMID:16543145

    Open questions at the time
    • Whether additional kinases phosphorylate MCL-1 at other sites to co-regulate turnover not resolved
    • Tissue-specific usage of this pathway not established
  8. 2006 High

    Conditional knockout of MCL-1 in myeloid and neutrophil lineages demonstrated that MCL-1 is non-redundantly required for neutrophil survival, with Bax/Bak co-deletion rescuing the phenotype, placing MCL-1 genetically upstream of the core apoptotic machinery in vivo.

    Evidence Lineage-specific conditional knockout mice, flow cytometry, genetic epistasis

    PMID:17062731 PMID:19064728

    Open questions at the time
    • Whether MCL-1 has non-apoptotic roles in neutrophils not examined
    • Compensatory upregulation in macrophages not mechanistically explained
  9. 2006 High

    TRAIL/caspase-8 cleavage of MCL-1 at the outer mitochondrial membrane was shown to release sequestered BIM for BAX activation, establishing a direct molecular connection between the extrinsic and intrinsic apoptosis pathways through MCL-1.

    Evidence RNAi, Co-IP, caspase activity assays, mitochondrial membrane potential measurement

    PMID:16478725

    Open questions at the time
    • Precise cleavage site(s) and fragment functions not fully characterized
    • In vivo relevance in TRAIL-responsive tumors untested
  10. 2009 High

    USP9X was identified as a deubiquitinase that removes K48-linked polyubiquitin from MCL-1 to stabilize it, and USP9X knockdown sensitized cells to ABT-737, revealing a druggable axis controlling MCL-1 turnover.

    Evidence In vitro deubiquitination reconstitution, Co-IP, RNAi, cycloheximide chase, xenograft model

    PMID:20023629

    Open questions at the time
    • Selectivity of USP9X for MCL-1 versus other substrates not determined
    • Context-dependence relative to other DUBs (Ku70, USP13) unclear
  11. 2010 High

    An MCL-1 mutant lacking all lysines was still degraded at wild-type rates, and purified MCL-1 was cleaved by the 20S proteasome in vitro, establishing a ubiquitin-independent degradation pathway that challenges the assumption that MCL-1 turnover is purely ubiquitin-driven.

    Evidence Lysine-less MCL-1 mutant, cell-free 20S proteasome assay, E1 inhibition, primary lymphocytes

    PMID:20385764

    Open questions at the time
    • Relative contribution of 20S versus 26S pathways under physiological conditions unknown
    • Structural features of MCL-1 making it a 20S substrate not mapped
  12. 2011 High

    SCF(FBW7) was shown to ubiquitinate MCL-1 in a GSK-3β-phosphorylation-dependent manner, and FBW7 loss in T-ALL caused MCL-1-dependent resistance to BH3 mimetics, providing a genetic explanation for therapy resistance in specific cancers.

    Evidence In vitro ubiquitination reconstitution, genetic rescue, pharmacological and shRNA manipulation

    PMID:21368833

    Open questions at the time
    • Hierarchy and cooperativity among Mule, FBW7, and other E3 ligases not resolved
    • Whether FBW7 mutations predict MCL-1 inhibitor sensitivity in patients unknown
  13. 2012 High

    Separation-of-function studies showed MCL-1 localizes to both the mitochondrial outer membrane (anti-apoptotic) and the mitochondrial matrix (promoting morphology and oxidative phosphorylation), establishing two mechanistically distinct roles at different submitochondrial compartments.

    Evidence Subcellular fractionation, mitochondrial import assays, conditional knockout, functional domain analysis

    PMID:23026029

    Open questions at the time
    • Mechanism of MCL-1 import into the matrix not determined
    • Substrates/partners for matrix MCL-1 function not identified
  14. 2013 High

    Cardiac-specific MCL-1 deletion caused lethal cardiomyopathy with defective mitochondrial respiration; Bax/Bak co-deletion rescued lethality but not mitochondrial defects, genetically proving that MCL-1's mitochondrial maintenance function is independent of apoptosis suppression.

    Evidence Conditional knockout mice, Bax/Bak co-deletion, electron microscopy, mitochondrial respiration assays, echocardiography

    PMID:23788622

    Open questions at the time
    • Molecular targets of matrix MCL-1 in cardiomyocytes unidentified
    • Whether matrix function is relevant in non-cardiac tissues unknown
  15. 2014 High

    Ku70 was discovered to function as a non-canonical deubiquitinase for MCL-1, removing K48-polyubiquitin chains and stabilizing MCL-1 at mitochondria and other compartments, broadening the repertoire of MCL-1-stabilizing DUBs beyond classical USP family members.

    Evidence Purified protein in vitro deubiquitination, Co-IP, knockout MEFs, subcellular fractionation, domain mapping

    PMID:24769731

    Open questions at the time
    • Structural basis for Ku70 deubiquitinase activity not resolved
    • Whether this is a canonical enzymatic activity or assisted unfolding unclear
  16. 2016 High

    An allosteric mechanism for MCL-1 inhibition was discovered: covalent modification of C286, distant from the BH3 groove, impaired BH3 binding and BAX suppression, identifying a druggable site distinct from the canonical groove.

    Evidence Covalent chemical modification, C286W mutagenesis, NMR, BH3-binding and BAX-suppression assays

    PMID:27159560

    Open questions at the time
    • Whether allosteric site is pharmacologically tractable for clinical inhibitors unknown
    • Structural dynamics linking C286 to groove rearrangement not fully modeled
  17. 2017 High

    MCL-1 was found to interact with the Ku heterodimer via BH1 and BH3 domains to inhibit NHEJ and promote HR-mediated DNA repair during S/G2, revealing a non-canonical nuclear function in DNA damage response pathway choice.

    Evidence Reciprocal Co-IP, BH1/BH3 domain mutagenesis, HR/NHEJ reporter assays, cell cycle analysis, xenograft

    PMID:29227281

    Open questions at the time
    • Whether nuclear MCL-1 function is relevant in non-cancerous contexts unknown
    • Mechanism of MCL-1 nuclear import/export not characterized
  18. 2017 High

    A mitochondrial-localization-defective MCL-1 mutant separated the bioenergetic role (enhancing OXPHOS and ROS) from anti-apoptotic function in triple-negative breast cancer stem cells, showing MYC and MCL-1 cooperate to maintain chemoresistant CSCs via mitochondrial metabolism.

    Evidence MCL-1 localization mutant, respiration assays, ROS measurement, tumor-initiation in vivo

    PMID:28978427

    Open questions at the time
    • Molecular mechanism by which matrix MCL-1 enhances OXPHOS still unknown
    • Generalizability beyond TNBC CSCs not established
  19. 2018 High

    APC/C was identified as an E3 ligase that degrades MCL-1 during prolonged mitotic arrest via a D-box motif, with a C-terminal IR tail converting MCL-1 into a checkpoint-independent substrate, providing a molecular timer for the slippage-versus-death decision in mitosis.

    Evidence Live-cell imaging, D-box and IR tail mutagenesis, siRNA depletion of APC/C components

    PMID:29987118

    Open questions at the time
    • Relative importance of APC/C versus SCF(FBW7) in mitotic MCL-1 degradation not compared
    • Whether this timer operates identically across cell types not tested
  20. 2021 High

    Erythroid-specific MCL-1 deletion demonstrated an essential anti-apoptotic role restricted to early definitive erythropoiesis, rescuable by Bax/Bak co-deletion or ectopic BCL-2, clarifying lineage-specific redundancy within the BCL-2 family.

    Evidence Erythroid-specific conditional knockout, genetic epistasis, BCL-2 rescue

    PMID:33512417

    Open questions at the time
    • Why MCL-1 is dispensable at later erythroid stages unknown
    • Whether matrix MCL-1 function contributes to erythropoiesis not addressed
  21. 2022 Medium

    MCL-1 was shown to promote selective mitophagy via LC3-interacting regions (LIR motifs) and interaction with Bnip3, while suppressing bulk autophagy, revealing a quality-control function that discriminates between general and organelle-targeted autophagic pathways.

    Evidence LIR motif mutagenesis, Co-IP with Bnip3, autophagy flux and mitophagy reporter assays in cardiac cells

    PMID:35563775

    Open questions at the time
    • Whether LIR-dependent mitophagy operates in non-cardiac tissues untested
    • Relationship between matrix MCL-1 and LIR-dependent mitophagy unclear
    • Single-lab finding awaiting independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular targets and mechanism by which matrix-localized MCL-1 promotes oxidative phosphorylation and mitochondrial morphology remain unidentified, and how the multiple E3 ligases, DUBs, and ubiquitin-independent degradation pathways are hierarchically coordinated across tissues and stress contexts is not resolved.
  • Matrix MCL-1 binding partners and substrates unidentified
  • Integrated model of E3/DUB hierarchy across tissues lacking
  • Structural basis for allosteric communication between C286 and BH3 groove incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140313 molecular sequestering activity 5 GO:0098772 molecular function regulator activity 2
Localization
GO:0005739 mitochondrion 6 GO:0005634 nucleus 1
Pathway
R-HSA-5357801 Programmed Cell Death 8 R-HSA-392499 Metabolism of proteins 5 R-HSA-1430728 Metabolism 2 R-HSA-1640170 Cell Cycle 2 R-HSA-73894 DNA Repair 1 R-HSA-9612973 Autophagy 1
Partners
BAK1BAXBCL2L11FBXW7HUWE1NOXAUSP9XXRCC5

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 MCL1 was originally identified as a gene induced early during phorbol ester-induced differentiation of the ML-1 human myeloid leukemia cell line along the monocyte/macrophage pathway, with sequence similarity to BCL2, establishing it as a founding member of the BCL-2 family associated with programming of differentiation and maintenance of cell viability. cDNA cloning, Northern blot, sequence analysis Proceedings of the National Academy of Sciences of the United States of America High 7682708
2005 Bak is sequestered in healthy cells specifically by Mcl-1 and Bcl-xL (but not Bcl-2, Bcl-w, or A1), requiring the Bak BH3 domain; BH3-only proteins such as Noxa can bind Mcl-1, displace Bak, and promote Mcl-1 degradation, but Bak-mediated death also requires neutralization of Bcl-xL. Co-immunoprecipitation, genetic rescue/epistasis, cell-free apoptosis assays Genes & development High 15901672
2005 BH3 domain peptides derived from Noxa selectively bind Mcl-1 (and A1) but not other prosurvival proteins, whereas Bad binds Bcl-2/Bcl-xL/Bcl-w but not Mcl-1, defining selective interaction specificity among BCL-2 family members; Bad and Noxa cooperate to kill cells by jointly neutralizing Mcl-1 and Bcl-2/Bcl-xL. Fluorescence polarization binding assays, Co-IP, cell death assays Molecular cell High 15694340
2005 BH3 peptides from Bid and Bim directly activate Bax, while other BH3 peptides (including those selective for Mcl-1) function as derepressors by relieving Mcl-1- or Bcl-xL-mediated inhibition of Bax, demonstrating that Mcl-1 acts upstream of Bax at mitochondrial membranes. Reconstituted membrane-permeabilization assay, BH3 peptide competition Molecular cell High 15721256
2005 TCTP (translationally controlled tumor protein) directly interacts with Mcl-1 and stabilizes it by interfering with ubiquitin-dependent proteasomal degradation; overexpression of TCTP augments Mcl-1 protein stability and antiapoptotic activity, while TCTP knockdown destabilizes Mcl-1; the TCTP-binding-defective Mcl-1 mutant K257V is more rapidly degraded and has compromised antiapoptotic function. Co-IP, RNAi knockdown, site-directed mutagenesis, cycloheximide chase, apoptosis assays Molecular and cellular biology High 15798198
2005 Mule (Mcl-1 ubiquitin ligase E3), a 482 kDa HECT-domain E3 ubiquitin ligase containing a BH3-like domain, directly binds Mcl-1 via its BH3 domain, polyubiquitinates Mcl-1 at five lysine residues, and is required for DNA damage-induced Mcl-1 degradation and apoptosis; RNAi depletion of Mule stabilizes Mcl-1 and attenuates DNA damage-induced apoptosis. Biochemical fractionation, in vitro ubiquitination assay, RNAi, Co-IP Cell High 15989957
2004 Mitochondrially localized p53 interacts with the proapoptotic protein Bak, causing Bak oligomerization and cytochrome c release; formation of the p53-Bak complex coincides with dissociation of the Bak-Mcl-1 complex, indicating that Mcl-1 normally sequesters Bak and that p53 can displace Mcl-1 to activate apoptosis. Co-IP from mitochondrial fractions, cell-free cytochrome c release assay Nature cell biology High 15077116
2006 Glycogen synthase kinase-3 (GSK-3) phosphorylates MCL-1 at S159, promoting its ubiquitination and proteasomal degradation upon IL-3 withdrawal; AKT inactivates GSK-3 to sustain MCL-1 levels and prevent apoptosis; the phosphorylation-site mutant MCL-1(S159A) shows enhanced stability and greater protection from apoptosis. In vitro kinase assay, site-directed mutagenesis, pharmacological inhibitors, cycloheximide chase, ubiquitination assay Molecular cell High 16543145
2006 MCL-1 inhibits mitochondrial Ca2+ signals induced by Ca2+ agonists or apoptotic stimuli (without affecting ER Ca2+ store size or IP3R expression), providing evidence that Mcl-1 acts directly at mitochondria to suppress Ca2+ uptake as a mechanism of apoptosis inhibition. Overexpression and siRNA knockdown with mitochondrial Ca2+ imaging The Journal of biological chemistry Medium 16027162
2006 BH3 profiling revealed that MCL-1 (along with BCL-2, BCL-XL, MCL-1, BFL-1, BCL-w) each bears a distinct pattern of interaction with BH3-domain peptides; cellular dependence on MCL-1 for survival correlates with sequestration of activator BH3-only proteins (BID or BIM) by MCL-1 at mitochondria. BH3 profiling (peptide-based mitochondrial permeabilization assay), Co-IP Cancer cell High 16697956
2006 TRAIL-activated caspase-8 or caspase-3 directly cleaves Mcl-1 at the mitochondrial outer membrane, freeing Bim (normally sequestered by Mcl-1) to mediate Bax-dependent apoptosis and release of cytochrome c, Smac, and HtrA2; this defines a novel TRAIL/caspase-8/Mcl-1/Bim communication between extrinsic and intrinsic apoptotic pathways. RNAi knockdown, Co-IP, mitochondrial membrane potential measurement, caspase activity assays The Journal of biological chemistry High 16478725
2003 UV irradiation blocks Mcl-1 protein synthesis and causes rapid proteasomal degradation of the existing Mcl-1 pool; elimination of Mcl-1 is required upstream of Bcl-xL translocation, Bax translocation, cytochrome c release, and caspase activation in UV-induced apoptosis. Genetic epistasis (Mcl-1 depletion), subcellular fractionation, proteasome inhibitor rescue, cell-free apoptosis assay Genes & development High 12783855
2009 USP9X (a deubiquitinase) binds MCL1 and removes Lys48-linked polyubiquitin chains that mark MCL1 for proteasomal degradation, thereby stabilizing MCL1 and promoting cell survival; USP9X knockdown increases MCL1 polyubiquitination and turnover, and sensitizes cells to the BH3 mimetic ABT-737. Co-IP, in vitro deubiquitination assay, RNAi, cycloheximide chase, xenograft Nature High 20023629
2007 In multiple myeloma cells treated with bortezomib, Mcl-1 is cleaved (in addition to accumulating as full-length protein); Noxa is strongly induced, Noxa-Mcl-1 complexes increase, Mcl-1/Bak complexes are disrupted, and Bim is displaced from Mcl-1 by Noxa, liberating Bim to activate Bax/Bak-dependent apoptosis. Co-IP, siRNA knockdown, immunoblotting, caspase activation assays Cancer research High 17545623
2010 MCL-1 can be degraded independently of ubiquitination: an MCL-1 mutant lacking all lysine residues (MCL-1(KR), incapable of ubiquitination) is still eliminated at the same rate as wild-type MCL-1 under basal and stressed conditions, and unmodified in vitro-translated MCL-1 can be degraded by the 20S proteasome in a cell-free system. Ubiquitin-deficient MCL-1 mutant (KR), cell-free 20S proteasome assay, E1 inhibition, primary lymphocyte experiments Molecular and cellular biology High 20385764
2011 SCF(FBW7) E3 ubiquitin ligase ubiquitylates MCL-1 in a GSK3-phosphorylation-dependent manner, targeting it for proteasomal destruction; loss of FBW7 in T-ALL leads to MCL-1 overexpression and resistance to the BCL-2 antagonist ABT-737, which is restored by FBW7 reconstitution or MCL-1 depletion. In vitro ubiquitination assay, Co-IP, genetic rescue, pharmacological inhibition, shRNA Nature High 21368833
2012 Trim17 is identified as an E3 ubiquitin ligase for Mcl-1 in neurons: Trim17 co-immunoprecipitates with Mcl-1, ubiquitinates Mcl-1 in vitro, and promotes phosphorylation-dependent (GSK3-mediated) proteasomal degradation of Mcl-1 to initiate neuronal apoptosis; knockdown of Trim17 reduces Mcl-1 ubiquitination and degradation. Co-IP, in vitro ubiquitination assay, GSK3 inhibition, site-directed mutagenesis, primary neuron cultures, RNAi Cell death and differentiation High 22976837
2013 Cardiac-specific ablation of Mcl-1 causes lethal dilated cardiomyopathy with loss of contractility, abnormal mitochondrial ultrastructure, and defective mitochondrial respiration; genetic co-deletion of Bax and Bak largely rescues lethality and cardiac function but does not fully restore mitochondrial morphology or respiration, indicating that MCL-1 has both antiapoptotic and a distinct mitochondrial function in cardiomyocytes. Conditional knockout mice, genetic epistasis (Bax/Bak co-deletion), electron microscopy, mitochondrial respiration assays, echocardiography Genes & development High 23788622
2012 MCL-1 promotes maintenance of normal mitochondrial morphology and energy production through localization to the mitochondrial matrix, while its antiapoptotic function is restricted to the outer mitochondrial membrane (OMM); these two functions depend on separate mitochondrial sublocalizations. Subcellular fractionation, mitochondrial import assays, functional domain analysis, conditional knockout Trends in cell biology High 23026029
2014 Ku70, a DNA double-strand break repair protein, functions as a deubiquitinase for Mcl-1: Ku70 directly binds Mcl-1 via its C-terminus (aa 536-609), co-localizes with Mcl-1 in mitochondria/ER/nucleus, and purified Ku70 directly removes K48-linked polyubiquitin chains from Mcl-1 in vitro, stabilizing Mcl-1 and suppressing apoptosis. Knockout MEFs, Co-IP, subcellular fractionation, in vitro deubiquitination with purified proteins, domain mapping, xenograft Cell death and differentiation High 24769731
2006 Conditional knockout of Mcl-1 in myeloid precursors causes neutropenia due to apoptotic death during granulocyte differentiation; this phenotype is rescued by co-deletion of Bax and Bak (but not Bim and Puma deletion or cytokine treatment), placing MCL-1's neutrophil survival function upstream of the Bax/Bak apoptotic pathway. In macrophages, MCL-1 loss increases apoptosis sensitivity during bacterial phagocytosis in a Bim-dependent manner. Lineage-specific conditional knockout mice, genetic epistasis, flow cytometry, bacterial phagocytosis assay Blood High 19064728
2006 Conditional deletion of Mcl-1 in neutrophils results in a ~2-3 fold higher apoptotic rate and severe defect in neutrophil survival in blood, spleen, and bone marrow; macrophage survival is normal and is associated with compensatory upregulation of Bcl-2 and Bcl-xL. Conditional knockout mice, flow cytometry apoptosis assays, immunoblotting Blood High 17062731
2007 Mcl-1 and Bim proteins mutually protect each other from ubiquitin-proteasome degradation through their direct interaction; disruption of the Mcl-1/Bim complex (by shRNA knockdown of either) leads to increased polyubiquitination and proteasomal degradation of the unliganded partner protein. shRNA stable knockdown, co-IP, ubiquitination analysis, immunoblotting Biochemical and biophysical research communications Medium 17681275
2016 MCL-1 is allosterically inhibited by covalent small-molecule modification of cysteine C286, a site distant from the BH3-binding groove; C286 modification impairs BH3-binding capacity and suppression of BAX, a phenomenon recapitulated by C286W mutagenesis in vitro and in mouse cells, establishing an allosteric mechanism for disrupting MCL-1's antiapoptotic activity. Covalent chemical modification, site-directed mutagenesis (C286W), BH3 binding assays, BAX suppression assay, NMR/structural analysis Nature structural & molecular biology High 27159560
2016 Mcl-1 acts as a functional switch in DNA double-strand break (DSB) repair pathway choice: Mcl-1 expression peaks in S/G2 phase, it directly interacts with the Ku heterodimer (via BH1 and BH3 domains) to inhibit Ku-mediated NHEJ, and promotes Mre11-dependent DNA resection and HR; Mcl-1 depletion reduces HR and enhances NHEJ. Co-IP, cell cycle analysis, domain mutagenesis (BH1, BH3), HR/NHEJ reporter assays, small molecule (MI-223) targeting BH1, in vivo xenograft The Journal of clinical investigation High 29227281
2018 APC/C (anaphase-promoting complex/cyclosome) mediates proteolytic destruction of Mcl-1 during prolonged mitotic arrest via a D-box motif; an IR (isoleucine-arginine) C-terminal tail converts Mcl-1 from a Cdc20-dependent (checkpoint-controlled) substrate to one degraded independently of checkpoint strength, providing a slow, steady apoptotic timer during mitosis that distinguishes prolonged arrest from normal mitosis. Live-cell imaging, D-box and IR tail mutagenesis, siRNA depletion of APC/C components, proteasome inhibition The EMBO journal High 29987118
2016 Mcl-1 overexpression extends the time from mitotic entry to mitotic exit in taxol-arrested cells, while Mcl-1 inhibition accelerates slippage; Mcl-1 competes with Cyclin B1 for binding to the proteasomal degradation machinery, slowing Cyclin B1 degradation and thereby influencing the slippage-versus-death decision during mitotic arrest. Overexpression/inhibition of Mcl-1, live-cell imaging, competition assays Oncotarget Medium 26769847
2007 Anoikis initiation requires Mcl-1 degradation via a GSK-3β-dependent proteasomal pathway upon matrix detachment, combined with transcriptional upregulation of Bim; Mcl-1 degradation in the presence of Bim is sufficient to induce anoikis, and oncogenic signaling (PI3K/Akt, MAPK) blocks this by suppressing Mcl-1 degradation and Bim induction. GSK-3β inhibition, proteasome inhibitors, RNAi knockdown, in vivo metastasis assays Cancer research High 18006817
2017 Hsp90 inhibition promotes GSK3β-dependent phosphorylation of Mcl-1, which then binds FBW7 and undergoes ubiquitination and proteasomal degradation; FBW7 mutations block this pathway and confer resistance to Hsp90 inhibitors; knock-in of a phosphorylation-defective Mcl-1 abrogates degradation and confers resistance in vitro and in vivo. Knock-in mutagenesis, Co-IP, ubiquitination assay, shRNA, xenograft models Molecular cancer therapeutics High 28619760
2017 FBXO4 is an E3 ubiquitin ligase that directly interacts with Mcl-1 and promotes its ubiquitination and proteasomal degradation; FBXO4 knockdown dramatically elevates Mcl-1 protein levels and increases cell survival and drug resistance, while FBXO4 overexpression has the opposite effect. Co-IP, in vitro ubiquitination assay, RNAi, overexpression, immunoblotting in patient samples Cancer gene therapy Medium 28776569
2002 Mcl-1 antisense oligonucleotides (but not Bcl-2 or Bcl-xL ASOs) trigger apoptosis in all tested human myeloma cell lines and primary myeloma cells, through disruption of mitochondrial membrane potential and caspase-3 activation, establishing Mcl-1 as the essential survival protein in multiple myeloma. Antisense oligonucleotides, flow cytometry (apoptosis, ΔΨm), caspase-3 activation assay Blood High 12070027
2012 Genetic removal of Mcl-1 (but not Bcl-xL, Bcl-2, or Bcl-w) is required for death of transformed AML cells and cures disease in AML-afflicted mice; enforced expression of selective inhibitors of Mcl-1 triggers death of human AML cells. Conditional knockout mice, shRNA, selective BH3 peptide expression, in vivo AML model Genes & development High 22279045
2013 In fludarabine-sensitive leukemic cells, MCL-1 degradation following drug treatment frees both BIM (proapoptotic) and BECN1 (autophagy initiator) from MCL-1 sequestration, triggering cell-death-associated autophagy; in fludarabine-resistant cells, low BIM and persistent BECN1 sequestration by MCL-1 prevents both apoptosis and BECN1-dependent autophagy. Co-IP (MCL-1/BIM, MCL-1/BECN1), siRNA, shRNA knockdowns, cell death assays in sensitive and resistant cell lines Cell death & disease Medium 23681223
2011 SRSF1 (and SRSF5) RNA-binding proteins regulate alternative splicing of Mcl-1 pre-mRNA; knockdown of SRSF1 shifts splicing between the anti-apoptotic Mcl-1L and pro-apoptotic Mcl-1S isoforms in a cell-context-dependent manner, and also affects Mcl-1 protein stability and translation. RNAi (siRNA knockdown), RT-PCR splicing assay, immunoblotting PloS one Medium 23284704
2018 hnRNP F, H1, and K bind specific sites in the Mcl-1 pre-mRNA and regulate alternative splicing toward Mcl-1L; siRNA-mediated knockdown of these hnRNPs switches splicing toward the proapoptotic Mcl-1S isoform and activates the mitochondrial cell death pathway, with triple knockdown producing up to 30-fold changes in Mcl-1S levels. siRNA knockdown, RNA immunoprecipitation, minigene construct splicing assay, flow cytometry RNA biology Medium 30468106
2015 Mcl-1 involvement in mitochondrial dynamics: increased Mcl-1S/L ratio (via splice-switching antisense oligonucleotides) induces mitochondrial hyperpolarization, increased mitochondrial Ca2+ accumulation, and Drp1-dependent mitochondrial hyperfusion, linking the Mcl-1 isoform balance to regulation of the mitochondrial fusion/fission machinery. Splice-switching antisense oligonucleotides, mitochondrial morphology imaging, Ca2+ measurement, Drp1 knockdown Molecular biology of the cell Medium 26538029
2017 MYC and MCL-1 cooperate to maintain chemotherapy-resistant cancer stem cells (CSCs) in TNBC by increasing mitochondrial oxidative phosphorylation (mtOXPHOS) and ROS generation; a mutant MCL-1 that cannot localize to mitochondria reduces mtOXPHOS and ROS without affecting MCL-1's antiapoptotic function, demonstrating that MCL-1's mitochondrial role in bioenergetics is mechanistically distinct from its apoptosis-suppressing role. MCL-1 localization mutant, mitochondrial respiration assay, ROS measurement, CSC assays, in vivo tumor initiation Cell metabolism High 28978427
2021 USP13 (a deubiquitinase) binds, deubiquitinates, and stabilizes Mcl-1 in cervical cancer cells; USP13 depletion or inhibition reduces Mcl-1 protein levels, inhibits cell proliferation, and sensitizes cells to ABT-263; USP13 and Mcl-1 protein levels positively correlate in cervical cancer tissue. Co-IP, deubiquitination assay, siRNA knockdown, pharmacological USP13 inhibition, IHC correlation Oncogene Medium 33627786
2022 Skp2 stabilizes Mcl-1 by competing with and blocking FBW7-mediated Mcl-1 ubiquitination and degradation; Skp2 depletion (via CRISPR-Cas9 KO) reduces Mcl-1 protein, sensitizes colorectal cancer cells to irradiation, and Skp2-Mcl-1 interaction was confirmed by co-IP. CRISPR-Cas9 knockout, Co-IP, ubiquitination analysis, in vitro and in vivo irradiation experiments Cell death & disease Medium 35301297
2022 TRAF4 stabilizes MCL-1 through an indirect mechanism: IR promotes TRAF4-Akt interaction leading to Akt K63-ubiquitination and activation; activated Akt phosphorylates and inhibits GSK3β, reducing MCL-1 S159 phosphorylation, which disrupts the MCL-1 interaction with JOSD1 deubiquitinase, preventing MCL-1 ubiquitination and degradation. Co-IP, ubiquitination analysis, TRAF4 knockout, GSK3β phosphorylation assays, site-directed mutagenesis, xenograft Cell death & disease Medium 36535926
2022 Mcl-1 suppresses starvation-induced non-selective autophagy but promotes selective mitophagy of depolarized mitochondria via its LC3-interacting regions (LIR motifs) and interaction with the mitophagy receptor Bnip3; the interaction between Mcl-1 and Bnip3 increases under mitochondrial stress, and mutation of LIR sites significantly reduces Mcl-1-mediated mitochondrial clearance. Cardiac-specific Mcl-1 overexpression, LIR motif mutagenesis, Co-IP with Bnip3, autophagy flux assays, mitophagy reporter Cells Medium 35563775
2021 Erythroid-specific Mcl1 deletion causes embryonic lethality from severe anemia; MCL-1 is required only during early definitive erythropoiesis; its function is antiapoptotic (co-deletion of Bax/Bak rescues the phenotype), and ectopic BCL2 expression can compensate for Mcl1 loss, indicating functional redundancy. Erythroid-specific conditional knockout, genetic epistasis (Bax/Bak co-deletion), ectopic BCL2 expression rescue Blood High 33512417
2018 Bim phosphorylation alters its binding to Mcl-1: constitutive Bim phosphorylation stabilizes Mcl-1 and primes it for death signals; phosphomimetic and phospho-deficient Bim mutations result in altered Mcl-1 stability and distinct antiapoptotic protein binding patterns, suggesting Bim phosphorylation regulates Mcl-1 dependence. Phosphomimetic/phospho-deficient Bim mutagenesis, Co-IP, cycloheximide chase stability assays The FEBS journal Medium 29775995
2014 STAT3 and MCL-1 are direct interacting partners during embryo implantation (confirmed by MALDI-TOF, far-western analysis, colocalization, and co-transfection); estrogen and progesterone regulate the interaction; in breast cancer cells overexpressing both proteins, the STAT3-MCL-1 association modulates normal anti-apoptotic activity of MCL-1 toward a pro-apoptotic outcome and decreases cellular invasion. MALDI-TOF, far-western analysis, co-IP, colocalization, co-transfection Journal of cell science Low 24481815
2011 A novel reverse BH3 (rBH3) motif was identified by phage display screening using Mcl-1's BH3-binding groove; rBH3 peptides bind the BH3 groove of Mcl-1 selectively over Bcl-xL as confirmed by NMR, fluorescence polarization, and alanine scanning, and proteins containing this motif represent previously unknown Mcl-1 binding partners. Phage display, NMR spectroscopy, fluorescence polarization displacement assay, alanine scanning The Journal of biological chemistry Medium 21953453

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2005 Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Molecular cell 1538 15694340
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2005 Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins. Genes & development 1059 15901672
2006 Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. Cancer cell 1049 16697956
2005 BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly. Molecular cell 973 15721256
1993 MCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2. Proceedings of the National Academy of Sciences of the United States of America 910 7682708
2006 Mechanisms of apoptosis sensitivity and resistance to the BH3 mimetic ABT-737 in acute myeloid leukemia. Cancer cell 885 17097560
1999 The proapoptotic activity of the Bcl-2 family member Bim is regulated by interaction with the dynein motor complex. Molecular cell 873 10198631
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2006 Glycogen synthase kinase-3 regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1. Molecular cell 731 16543145
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2005 Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis. Cell 703 15989957
2004 Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex. Nature cell biology 661 15077116
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2011 Global landscape of HIV-human protein complexes. Nature 593 22190034
2011 SCF(FBW7) regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction. Nature 565 21368833
2007 Small molecule obatoclax (GX15-070) antagonizes MCL-1 and overcomes MCL-1-mediated resistance to apoptosis. Proceedings of the National Academy of Sciences of the United States of America 551 18040043
2009 Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival. Nature 533 20023629
2017 MYC and MCL1 Cooperatively Promote Chemotherapy-Resistant Breast Cancer Stem Cells via Regulation of Mitochondrial Oxidative Phosphorylation. Cell metabolism 511 28978427
2003 Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation. Genes & development 511 12783855
2011 Bcl-x(L) retrotranslocates Bax from the mitochondria into the cytosol. Cell 505 21458670
2010 Effects of microRNA-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma. Hepatology (Baltimore, Md.) 501 20041405
2001 Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V actin motor complex, activated by anoikis. Science (New York, N.Y.) 501 11546872
2010 Mcl-1; the molecular regulation of protein function. FEBS letters 451 20540941
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2017 Synergistic drug combinations for cancer identified in a CRISPR screen for pairwise genetic interactions. Nature biotechnology 378 28319085
2002 Antisense strategy shows that Mcl-1 rather than Bcl-2 or Bcl-x(L) is an essential survival protein of human myeloma cells. Blood 361 12070027
2012 Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia. Genes & development 348 22279045
1998 Elevated expression of the apoptotic regulator Mcl-1 at the time of leukemic relapse. Blood 299 9446661
2021 Targeting MCL-1 in cancer: current status and perspectives. Journal of hematology & oncology 239 33883020
2006 The antiapoptotic protein Mcl-1 is essential for the survival of neutrophils but not macrophages. Blood 239 17062731
2013 Deletion of MCL-1 causes lethal cardiac failure and mitochondrial dysfunction. Genes & development 218 23788622
2007 Noxa up-regulation and Mcl-1 cleavage are associated to apoptosis induction by bortezomib in multiple myeloma. Cancer research 212 17545623
2005 Mcl-1. The international journal of biochemistry & cell biology 208 15474972
2005 Stabilization and enhancement of the antiapoptotic activity of mcl-1 by TCTP. Molecular and cellular biology 196 15798198
2012 Delving deeper: MCL-1's contributions to normal and cancer biology. Trends in cell biology 190 23026029
2020 Targeting MCL-1 in hematologic malignancies: Rationale and progress. Blood reviews 168 32204955
2008 Unique biology of Mcl-1: therapeutic opportunities in cancer. Current molecular medicine 164 18336294
2011 Targeting Mcl-1 for the therapy of cancer. Expert opinion on investigational drugs 160 21851287
2006 Interrelated roles for Mcl-1 and BIM in regulation of TRAIL-mediated mitochondrial apoptosis. The Journal of biological chemistry 157 16478725
2014 Mcl-1 ubiquitination: unique regulation of an essential survival protein. Cells 156 24814761
2014 Small molecule Mcl-1 inhibitors for the treatment of cancer. Pharmacology & therapeutics 140 25172548
2004 VEGF induces Mcl-1 up-regulation and protects multiple myeloma cells against apoptosis. Blood 131 15217829
2020 Saga of Mcl-1: regulation from transcription to degradation. Cell death and differentiation 125 31907390
2004 Mcl-1 regulation and its role in multiple myeloma. Cell cycle (Georgetown, Tex.) 120 15467463
2009 Mcl-1 is required for melanoma cell resistance to anoikis. Molecular cancer research : MCR 114 19372583
2015 Mcl-1 involvement in mitochondrial dynamics is associated with apoptotic cell death. Molecular biology of the cell 111 26538029
2018 MCL-1 inhibition in cancer treatment. OncoTargets and therapy 106 30425521
2010 Ubiquitin-independent degradation of antiapoptotic MCL-1. Molecular and cellular biology 106 20385764
2019 Recent advances in the development of Mcl-1 inhibitors for cancer therapy. Pharmacology & therapeutics 104 30790641
2008 Selective roles for antiapoptotic MCL-1 during granulocyte development and macrophage effector function. Blood 98 19064728
2022 Single-cell transcriptomics identifies Mcl-1 as a target for senolytic therapy in cancer. Nature communications 94 35449130
2007 Anoikis, initiated by Mcl-1 degradation and Bim induction, is deregulated during oncogenesis. Cancer research 86 18006817
2004 Regulation of neutrophil apoptosis by Mcl-1. Biochemical Society transactions 85 15157168
2006 Suppression of Mcl-1 via RNA interference sensitizes human hepatocellular carcinoma cells towards apoptosis induction. BMC cancer 84 17014711
2020 Discovery of S64315, a Potent and Selective Mcl-1 Inhibitor. Journal of medicinal chemistry 82 33146521
2009 Inhibition of MCL-1 enhances lapatinib toxicity and overcomes lapatinib resistance via BAK-dependent autophagy. Cancer biology & therapy 81 19823038
2019 Multiple myeloma with 1q21 amplification is highly sensitive to MCL-1 targeting. Blood advances 79 31856269
2012 Regulation of Mcl-1 by SRSF1 and SRSF5 in cancer cells. PloS one 78 23284704
2012 Trim17-mediated ubiquitination and degradation of Mcl-1 initiate apoptosis in neurons. Cell death and differentiation 77 22976837
2019 Molecular Comprehension of Mcl-1: From Gene Structure to Cancer Therapy. Trends in cell biology 76 31030977
2011 Mcl-1 ubiquitination and destruction. Oncotarget 73 21608150
2011 Regulation of neutrophil survival/apoptosis by Mcl-1. TheScientificWorldJournal 72 22125448
2020 Development of Mcl-1 inhibitors for cancer therapy. European journal of medicinal chemistry 62 33333396
2016 Mcl-1 dynamics influence mitotic slippage and death in mitosis. Oncotarget 62 26769847
2014 Role of Ku70 in deubiquitination of Mcl-1 and suppression of apoptosis. Cell death and differentiation 62 24769731
2003 Transcriptional and translational control of Mcl-1 during apoptosis. Archives of biochemistry and biophysics 62 12941295
2020 Mcl-1 inhibition overcomes intrinsic and acquired regorafenib resistance in colorectal cancer. Theranostics 60 32724460
2006 Regulation of Mcl-1 expression in rheumatoid arthritis synovial macrophages. Arthritis and rheumatism 60 17009247
2017 FBW7-Dependent Mcl-1 Degradation Mediates the Anticancer Effect of Hsp90 Inhibitors. Molecular cancer therapeutics 58 28619760
2005 The anti-apoptotic protein Mcl-1 inhibits mitochondrial Ca2+ signals. The Journal of biological chemistry 58 16027162
2019 Hot-Spots of Mcl-1 Protein. Journal of medicinal chemistry 57 31580668
2016 Dual modulation of MCL-1 and mTOR determines the response to sunitinib. The Journal of clinical investigation 56 27893461
2008 Downregulation of Mcl-1 potentiates HDACi-mediated apoptosis in leukemic cells. Leukemia 55 18239621
2017 Targeting Mcl-1 enhances DNA replication stress sensitivity to cancer therapy. The Journal of clinical investigation 54 29227281
2016 Intersection of mitochondrial fission and fusion machinery with apoptotic pathways: Role of Mcl-1. Biology of the cell 54 27234233
2023 Targeting MCL-1 protein to treat cancer: opportunities and challenges. Frontiers in oncology 53 37601693
2015 Mcl-1 is an important therapeutic target for oral squamous cell carcinomas. Oncotarget 53 26009874
2019 Structure-Guided Discovery of a Selective Mcl-1 Inhibitor with Cellular Activity. Journal of medicinal chemistry 51 31339316
2018 Small-molecule Mcl-1 inhibitors: Emerging anti-tumor agents. European journal of medicinal chemistry 51 29407973
2016 Allosteric inhibition of antiapoptotic MCL-1. Nature structural & molecular biology 51 27159560
2016 BRAFV600E-dependent Mcl-1 stabilization leads to everolimus resistance in colon cancer cells. Oncotarget 51 27351224
2020 MCL-1 gains occur with high frequency in lung adenocarcinoma and can be targeted therapeutically. Nature communications 50 32913197
2019 MCL-1 inhibitors - where are we now (2019)? Expert opinion on therapeutic patents 49 31566022
2018 Bicyclic Helical Peptides as Dual Inhibitors Selective for Bcl2A1 and Mcl-1 Proteins. Journal of medicinal chemistry 49 29584430
2020 AMG-176, an Mcl-1 Antagonist, Shows Preclinical Efficacy in Chronic Lymphocytic Leukemia. Clinical cancer research : an official journal of the American Association for Cancer Research 48 31937611
2011 MCL-1 regulates the balance between autophagy and apoptosis. Autophagy 48 21412051
2018 Myeloid-Specific Deletion of Mcl-1 Yields Severely Neutropenic Mice That Survive and Breed in Homozygous Form. Journal of immunology (Baltimore, Md. : 1950) 47 30464050
2020 Pairing MCL-1 inhibition with venetoclax improves therapeutic efficiency of BH3-mimetics in AML. European journal of haematology 46 32659848
2015 Early downregulation of Mcl-1 regulates apoptosis triggered by cardiac glycoside UNBS1450. Cell death & disease 46 26068790
2016 Structure Based Design of Non-Natural Peptidic Macrocyclic Mcl-1 Inhibitors. ACS medicinal chemistry letters 44 28197319
2021 The deubiquitinase (DUB) USP13 promotes Mcl-1 stabilisation in cervical cancer. Oncogene 43 33627786
2014 Modulation of Mcl-1 sensitizes glioblastoma to TRAIL-induced apoptosis. Apoptosis : an international journal on programmed cell death 43 24213561
2013 Hydroxyquinoline-derived compounds and analoguing of selective Mcl-1 inhibitors using a functional biomarker. Bioorganic & medicinal chemistry 43 23993674
2012 Ouabain downregulates Mcl-1 and sensitizes lung cancer cells to TRAIL-induced apoptosis. American journal of physiology. Cell physiology 42 23174563
2022 Skp2 stabilizes Mcl-1 and confers radioresistance in colorectal cancer. Cell death & disease 41 35301297
2018 Regulation of Mcl-1 alternative splicing by hnRNP F, H1 and K in breast cancer cells. RNA biology 40 30468106
2021 Breast cancer dependence on MCL-1 is due to its canonical anti-apoptotic function. Cell death and differentiation 37 33785871
2015 Sorafenib Inhibition of Mcl-1 Accelerates ATRA-Induced Apoptosis in Differentiation-Responsive AML Cells. Clinical cancer research : an official journal of the American Association for Cancer Research 37 26459180
2013 BECN1 and BIM interactions with MCL-1 determine fludarabine resistance in leukemic B cells. Cell death & disease 35 23681223
2003 IL-6-independent expression of Mcl-1 in human multiple myeloma. Oncogene 35 12660820
2019 Transcriptional Silencing of MCL-1 Through Cyclin-Dependent Kinase Inhibition in Acute Myeloid Leukemia. Frontiers in oncology 34 31921615
2018 Atypical APC/C-dependent degradation of Mcl-1 provides an apoptotic timer during mitotic arrest. The EMBO journal 34 29987118
2016 miR-153 regulates apoptosis and autophagy of cardiomyocytes by targeting Mcl-1. Molecular medicine reports 34 27220418
2016 Survival control of malignant lymphocytes by anti-apoptotic MCL-1. Leukemia 34 27479182
2011 Identification of a novel Mcl-1 protein binding motif. The Journal of biological chemistry 34 21953453
2017 FBXO4 inhibits lung cancer cell survival by targeting Mcl-1 for degradation. Cancer gene therapy 33 28776569
2017 Promoting Vaginal Distribution of E7 and MCL-1 siRNA-Silencing Nanoparticles for Cervical Cancer Treatment. Molecular pharmaceutics 32 28350964
2013 Oncogenic BRAF signalling increases Mcl-1 expression in cutaneous metastatic melanoma. Experimental dermatology 32 24118207
2020 Cotargeting BCL-2 and MCL-1 in high-risk B-ALL. Blood advances 31 32569380
2020 Discovery of a Copper-Based Mcl-1 Inhibitor as an Effective Antitumor Agent. Journal of medicinal chemistry 31 32794745
2009 Mcl-1 functions as major epidermal survival protein required for proper keratinocyte differentiation. The Journal of investigative dermatology 31 19037233
2019 Degradation of MCL-1 by bufalin reverses acquired resistance to osimertinib in EGFR-mutant lung cancer. Toxicology and applied pharmacology 30 31301315
1996 Immunohistochemical localization of Mcl-1 and bcl-2 proteins in thymic epithelial tumours. Histopathology 29 8971561
2021 Design, Synthesis, and Structural Characterization of Lysine Covalent BH3 Peptides Targeting Mcl-1. Journal of medicinal chemistry 28 33797903
2019 Ceramide Analogue SACLAC Modulates Sphingolipid Levels and MCL-1 Splicing to Induce Apoptosis in Acute Myeloid Leukemia. Molecular cancer research : MCR 28 31744877
2007 Reciprocal protection of Mcl-1 and Bim from ubiquitin-proteasome degradation. Biochemical and biophysical research communications 27 17681275
2017 The combination of reduced MCL-1 and standard chemotherapeutics is tolerable in mice. Cell death and differentiation 26 28800129
2019 Targeting KPNB1 overcomes TRAIL resistance by regulating DR5, Mcl-1 and FLIP in glioblastoma cells. Cell death & disease 24 30742128
2018 Phosphorylation alters Bim-mediated Mcl-1 stabilization and priming. The FEBS journal 24 29775995
2022 Mcl-1 Differentially Regulates Autophagy in Response to Changes in Energy Status and Mitochondrial Damage. Cells 23 35563775
2015 AML sensitivity to YM155 is modulated through AKT and Mcl-1. Cancer letters 23 26118775
2014 STAT3 and MCL-1 associate to cause a mesenchymal epithelial transition. Journal of cell science 22 24481815
2022 Stabilization of MCL-1 by E3 ligase TRAF4 confers radioresistance. Cell death & disease 21 36535926
2016 Dual inhibition of Mcl-1 by the combination of carfilzomib and TG02 in multiple myeloma. Cancer biology & therapy 21 27246906
2021 Inhibition of the anti-apoptotic protein MCL-1 severely suppresses human hematopoiesis. Haematologica 20 33241675
2021 Requirement for antiapoptotic MCL-1 during early erythropoiesis. Blood 20 33512417