Target Interacting Protein Information

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Target General Information
Target Interacting Proteins
References
Target General Information  Top
Target ID T14912 Target Info
Target Name Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)
Synonyms mcl1/EAT; Bcl2-L-3; Bcl-2-related protein EAT/mcl1; Bcl-2-like protein 3; BCL2L3
Target Type Clinical trial Target
Gene Name MCL1
Biochemical Class B-cell lymphoma Bcl-2
UniProt ID
MCL1_HUMAN 
Target Interacting Proteins  Top
Acyltransferases [+] 1 Acyltransferases +
Interacting Protein Name E3 ubiquitin-protein ligase HUWE1 (HUWE1) Interacting Protein Interacting Protein Info
UniProt ID
HUWE1_HUMAN 
Synonyms ARF.BP1; HECTH9; HSPC272; Ib772; LASU1; MULE; URE.B1; UREB1
Evidence Score (E-score) 11 Experimental Evidences +
1 Affinity Capture-Western [1]
2 Affinity Capture-Western [2]
3 Affinity Capture-Western [3]
4 Affinity Capture-Western [4]
5 Affinity Capture-Western [5]
6 Affinity Capture-Western [6]
7 Affinity Capture-Western [7]
8 Affinity Capture-Western [8]
9 Affinity Capture-Western [9]
10 Affinity Capture-Western [10]
11 Reconstituted Complex [11]
Alpha-type channels [+] 2 Alpha-type channels +
Interacting Target Name Apoptosis regulator BAK (BAK) Literature-reported Target Interacting Protein Info
UniProt ID
BAK_HUMAN 
Synonyms CDN1; Bcl-2-like protein 7; Bcl2like protein 7; Bcl2-L-7; Bcl2L7; Bcl-2 homologous antagonist/killer; Bcl2 homologous antagonist/killer
Evidence Score (E-score) 12 Experimental Evidences +
1 Affinity Capture-MS [12]
2 Affinity Capture-MS [13]
3 Affinity Capture-Western [14]
4 Affinity Capture-Western [15]
5 Affinity Capture-Western [16]
6 Affinity Capture-Western [2]
7 Affinity Capture-Western [17]
8 Protein-peptide [16]
9 Reconstituted Complex [14]
10 Reconstituted Complex [18]
11 Reconstituted Complex [11]
12 Reconstituted Complex [19]
Interacting Protein Name Apoptosis regulator BAX (BAX) Interacting Protein Interacting Protein Info
UniProt ID
BAX_HUMAN 
Synonyms BCL2L4
Evidence Score (E-score) 4 Experimental Evidences +
1 Affinity Capture-MS [12]
2 Affinity Capture-MS [13]
3 Affinity Capture-Western [2]
4 Affinity Capture-Western [20]
Auxiliary transporters [+] 2 Auxiliary transporters +
Interacting Protein Name Bcl-2-like protein 11 (BCL2L11) Interacting Protein Interacting Protein Info
UniProt ID
B2L11_HUMAN 
Synonyms BAM; BIM; BOD
Evidence Score (E-score) 11 Experimental Evidences +
1 Affinity Capture-Western [21]
2 Affinity Capture-Western [15]
3 Affinity Capture-Western [22]
4 Affinity Capture-Western [2]
5 Affinity Capture-Western [17]
6 Affinity Capture-Western [23]
7 Affinity Capture-Western [3]
8 Affinity Capture-Western [4]
9 Protein-peptide [24]
10 Protein-peptide [22]
11 Reconstituted Complex [11]
Interacting Protein Name Bcl2-associated agonist of cell death (BAD) Interacting Protein Interacting Protein Info
UniProt ID
BAD_HUMAN 
Synonyms BBC2; BCL2L8
Evidence Score (E-score) 2 Experimental Evidences +
1 Protein-peptide [25]
2 Yeast two hybrid [26]
Other proteins [+] 5 Other proteins +
Interacting Protein Name Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) Interacting Protein Interacting Protein Info
UniProt ID
APR_HUMAN 
Synonyms APR; NOXA
Evidence Score (E-score) 11 Experimental Evidences +
1 Affinity Capture-Western [27]
2 Affinity Capture-Western [28]
3 Affinity Capture-Western [2]
4 Affinity Capture-Western [17]
5 Affinity Capture-Western [10]
6 Affinity Capture-Western [29]
7 Affinity Capture-Western [30]
8 Co-localization [10]
9 Protein-peptide [24]
10 Protein-peptide [22]
11 Reconstituted Complex [11]
Interacting Protein Name Bcl-2-binding component 3 (BBC3) Interacting Protein Interacting Protein Info
UniProt ID
BBC3B_HUMAN 
Synonyms JFY.1; JFY1; PUMA
Evidence Score (E-score) 7 Experimental Evidences +
1 Affinity Capture-MS [12]
2 Affinity Capture-MS [13]
3 Affinity Capture-Western [31]
4 Co-localization [31]
5 Protein-peptide [24]
6 Protein-peptide [22]
7 Reconstituted Complex [11]
Interacting Protein Name BH3-interacting domain death agonist (BID) Interacting Protein Interacting Protein Info
UniProt ID
BID_HUMAN 
Synonyms FP497
Evidence Score (E-score) 6 Experimental Evidences +
1 Affinity Capture-Western [18]
2 Affinity Capture-Western [32]
3 Protein-peptide [25]
4 Protein-peptide [22]
5 Reconstituted Complex [18]
6 Reconstituted Complex [11]
Interacting Target Name F-box and WD-40 domain protein 7 (Fbxw7) Literature-reported Target Interacting Protein Info
UniProt ID
FBXW7_HUMAN 
Synonyms SEL-10; SEL10; hCdc4; hAgo; FBX30; FBW7; F-box-WD40 repeat protein 6; F-box/WD repeat-containing protein 7; F-box protein Fbxw6; F-box protein FBX30; F-box protein FBW7; F-box and WD-40 domain-containing protein 7; Archipelago homolog
Evidence Score (E-score) 4 Experimental Evidences +
1 Affinity Capture-Western [31]
2 Affinity Capture-Western [33]
3 Affinity Capture-Western [34]
4 Co-localization [31]
Interacting Protein Name Bcl-2-interacting killer (BIK) Interacting Protein Interacting Protein Info
UniProt ID
BIK_HUMAN 
Synonyms BIP1; BP4; NBK
Evidence Score (E-score) 3 Experimental Evidences +
1 Protein-peptide [25]
2 Protein-peptide [22]
3 Reconstituted Complex [11]
References  Top
REF 1 Noxa controls Mule-dependent Mcl-1 ubiquitination through the regulation of the Mcl-1/USP9X interaction. Biochem Biophys Res Commun. 2011 Sep 30;413(3):460-4.
REF 2 Regulation of heat-induced apoptosis by Mcl-1 degradation and its inhibition by Hsp70. Cell Death Differ. 2009 Apr;16(4):638-47.
REF 3 Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis. Cell. 2005 Jul 1;121(7):1085-95.
REF 4 Role of bile salt in regulating Mcl-1 phosphorylation and chemoresistance in hepatocellular carcinoma cells. Mol Cancer. 2011 Apr 20;10:44.
REF 5 Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival. Nature. 2010 Jan 7;463(7277):103-7.
REF 6 Reduced association of anti-apoptotic protein Mcl-1 with E3 ligase Mule increases the stability of Mcl-1 in breast cancer cells. Br J Cancer. 2011 Jul 26;105(3):428-37.
REF 7 A cardinal role for cathepsin d in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci. PLoS Pathog. 2011 Jan 27;7(1):e1001262.
REF 8 The double life of MULE in preeclamptic and IUGR placentae. Cell Death Dis. 2012 May 3;3:e305.
REF 9 Quantitative Lys--Gly-Gly (diGly) proteomics coupled with inducible RNAi reveals ubiquitin-mediated proteolysis of DNA damage-inducible transcript 4 (DDIT4) by the E3 ligase HUWE1. J Biol Chem. 2014 Oct 17;289(42):28942-55.
REF 10 Ursolic acid facilitates apoptosis in rheumatoid arthritis synovial fibroblasts by inducing SP1-mediated Noxa expression and proteasomal degradation of Mcl-1. FASEB J. 2018 May 25:fj201800425R.
REF 11 Mitochondrion-dependent N-terminal processing of outer membrane Mcl-1 protein removes an essential Mule/Lasu1 protein-binding site. J Biol Chem. 2011 Jul 15;286(28):25098-107.
REF 12 Architecture of the human interactome defines protein communities and disease networks. Nature. 2017 May 25;545(7655):505-509.
REF 13 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell. 2015 Jul 16;162(2):425-440.
REF 14 Mitochondrial p53 activates Bak and causes disruption of a Bak-Mcl1 complex. Nat Cell Biol. 2004 May;6(5):443-50.
REF 15 Anti-apoptotic Bcl-2 fails to form efficient complexes with pro-apoptotic Bak to protect from Celecoxib-induced apoptosis. Biochem Pharmacol. 2011 Jan 1;81(1):32-42.
REF 16 Proapoptotic Bak is sequestered by Mcl-1 and Bcl-xL, but not Bcl-2, until displaced by BH3-only proteins. Genes Dev. 2005 Jun 1;19(11):1294-305.
REF 17 MLN4924 induces Noxa upregulation in acute myelogenous leukemia and synergizes with Bcl-2 inhibitors. Cell Death Differ. 2015 Dec;22(12):2133-42.
REF 18 Specific cleavage of Mcl-1 by caspase-3 in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in Jurkat leukemia T cells. J Biol Chem. 2005 Mar 18;280(11):10491-500.
REF 19 TRAF6 Restricts p53 Mitochondrial Translocation, Apoptosis, and Tumor Suppression. Mol Cell. 2016 Nov 17;64(4):803-814.
REF 20 Synergistic antitumor activity of gemcitabine and ABT-737 in vitro and in vivo through disrupting the interaction of USP9X and Mcl-1. Mol Cancer Ther. 2011 Jul;10(7):1264-75.
REF 21 Refining the minimal sequence required for ERK1/2-dependent poly-ubiquitination and proteasome-dependent turnover of BIM. Cell Signal. 2010 May;22(5):801-8.
REF 22 Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. Cancer Cell. 2006 May;9(5):351-65.
REF 23 EPOX inhibits angiogenesis by degradation of Mcl-1 through ERK inactivation. Clin Cancer Res. 2009 Aug 1;15(15):4904-14.
REF 24 BH3 domains of BH3-only proteins differentially regulate Bax-mediated mitochondrial membrane permeabilization both directly and indirectly. Mol Cell. 2005 Feb 18;17(4):525-35.
REF 25 Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function. Mol Cell. 2005 Feb 4;17(3):393-403.
REF 26 Underphosphorylated BAD interacts with diverse antiapoptotic Bcl-2 family proteins to regulate apoptosis. Apoptosis. 2001 Oct;6(5):319-30.
REF 27 Antiproliferative and proapoptotic activity of GUT-70 mediated through potent inhibition of Hsp90 in mantle cell lymphoma. Br J Cancer. 2011 Jan 4;104(1):91-100.
REF 28 Obatoclax and lapatinib interact to induce toxic autophagy through NOXA. Mol Pharmacol. 2012 Apr;81(4):527-40.
REF 29 NOXA, a sensor of proteasome integrity, is degraded by 26S proteasomes by an ubiquitin-independent pathway that is blocked by MCL-1. Cell Death Differ. 2012 Sep;19(9):1424-34.
REF 30 The stress protein BAG3 stabilizes Mcl-1 protein and promotes survival of cancer cells and resistance to antagonist ABT-737. J Biol Chem. 2013 Mar 8;288(10):6980-90.
REF 31 Mcl-1 Degradation Is Required for Targeted Therapeutics to Eradicate Colon Cancer Cells. Cancer Res. 2017 May 1;77(9):2512-2521.
REF 32 Mechanism of apoptosis induction by inhibition of the anti-apoptotic BCL-2 proteins. Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20327-32.
REF 33 Targeting FBW7 as a Strategy to Overcome Resistance to Targeted Therapy in Non-Small Cell Lung Cancer. Cancer Res. 2017 Jul 1;77(13):3527-3539.
REF 34 FBW7-Dependent Mcl-1 Degradation Mediates the Anticancer Effect of Hsp90 Inhibitors. Mol Cancer Ther. 2017 Sep;16(9):1979-1988.

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