Affinage

MTTP

Microsomal triglyceride transfer protein large subunit · UniProt P55157

Round 2 corrected
Length
894 aa
Mass
99.4 kDa
Annotated
2026-04-29
130 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MTTP encodes the large (~88 kDa) subunit of microsomal triglyceride transfer protein, an ER-luminal heterodimer with protein disulfide isomerase (PDI) that transfers triglyceride, cholesteryl ester, and phospholipid to nascent apolipoprotein B during lipoprotein assembly, thereby controlling the number of apoB-containing particles secreted by hepatocytes and enterocytes (PMID:9106493, PMID:8876250, PMID:9211060). Loss-of-function mutations in MTTP cause abetalipoproteinemia, confirmed by absent MTP activity in patient tissues and by identification of homozygous truncating and missense mutations across multiple cohorts (PMID:1439810, PMID:8361539, PMID:8533758). MTP transcription is positively regulated by HNF-4α/HNF-1α and FoxO1 and repressed by the bile acid–FXR–SHP axis, the CLOCK–SHP circadian circuit, insulin signaling through MAPKerk, and post-transcriptionally by miR-30c-mediated mRNA degradation and intestine-specific IRE1β-dependent mRNA decay, while the IRE1α–XBP1s–PDI axis supports MTP activity in liver (PMID:7961826, PMID:18497885, PMID:15337761, PMID:20674862, PMID:23749231, PMID:18460335, PMID:23040069). Beyond canonical lipoprotein assembly, an alternative-promoter-driven MTP isoform transfers phospholipid to CD1d in thymocytes and antigen-presenting cells, a function required for NKT cell development (PMID:17312007).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1992 High

    Identification that MTP activity and its large subunit are absent in abetalipoproteinemia patients established MTP as essential for lipoprotein assembly and pinpointed the molecular defect underlying ABL.

    Evidence MTP activity assay and immunodetection in intestinal biopsies from ABL patients versus controls

    PMID:1439810

    Open questions at the time
    • Precise molecular identity and sequence of the large subunit not yet known
    • Mechanism of lipid transfer not resolved
  2. 1993 High

    Cloning of the MTP large subunit cDNA and identification of loss-of-function mutations in ABL patients proved the gene is causative for ABL and revealed structural homology to vitellogenin, suggesting a lipid-binding cavity architecture; mutagenesis demonstrated the C-terminal domain is required for triglyceride transfer activity.

    Evidence cDNA cloning, patient mutation identification, site-directed mutagenesis, COS-1 cell expression and activity assay

    PMID:8111381 PMID:8361539

    Open questions at the time
    • No crystal structure to define lipid-binding cavity directly
    • Heterodimer formation requirements not yet mapped
  3. 1994 High

    Dissection of the MTP promoter revealed cell-type-specific regulation by HNF-1 and HNF-4, a sterol response element, and a negative insulin response element, explaining tissue-restricted expression in liver and intestine.

    Evidence Promoter deletion analysis, luciferase reporter assays in liver, intestinal, and non-expressing cell lines

    PMID:7961826

    Open questions at the time
    • In vivo relevance of each promoter element not tested
    • Post-transcriptional regulation not yet explored
  4. 1996 High

    Pharmacological inhibition of MTP with a specific small molecule (BMS-200150) demonstrated that neutral lipid transfer activity is mechanistically required for apoB-containing lipoprotein secretion, rather than just correlated with it.

    Evidence In vitro lipid transfer assay, direct binding measurement, apoB secretion assay in HepG2 cells with MTP inhibitor

    PMID:8876250

    Open questions at the time
    • Structural basis of inhibitor binding unknown
    • In vivo pharmacokinetics not established
  5. 1997 High

    Biochemical characterization established MTP as an ER-luminal heterodimer of the unique 88 kDa subunit with PDI that transfers TG, CE, and PL, and showed MTP controls particle number rather than lipid composition.

    Evidence Biochemical purification and reconstituted lipid transfer assays; pharmacological and expression studies in hepatoma cells

    PMID:9106493 PMID:9211060

    Open questions at the time
    • Mechanism by which PDI contributes to transfer activity not defined
    • Structural basis of lipid substrate selectivity unknown
  6. 2004 High

    The HNF-4α→HNF-1α transcriptional axis was shown to directly activate MTP, while the bile acid–FXR–SHP pathway suppresses MTP by inhibiting HNF-4α at the promoter, connecting bile acid signaling to VLDL output.

    Evidence ChIP, siRNA knockdown, dominant-negative constructs, MTP promoter-luciferase in HepG2 cells

    PMID:15337761

    Open questions at the time
    • In vivo validation in FXR or SHP knockout liver not yet performed in this study
    • Contribution of SHP-independent FXR effects not ruled out
  7. 2007 High

    Discovery of an alternative-promoter-driven MTP isoform in thymocytes and APCs that transfers phospholipid to CD1d established a non-canonical function of MTP in NKT cell development, independent of apoB-lipoprotein assembly.

    Evidence Identification of MTPv1 splice variant, in vitro phospholipid transfer to CD1d, fetal thymic organ culture with MTP antagonists and NKT cell quantification

    PMID:17312007

    Open questions at the time
    • Lipid species loaded onto CD1d by MTP in vivo not fully characterized
    • Whether MTPv1 also transfers neutral lipids in immune cells not tested
  8. 2008 High

    Two opposing post-transcriptional and transcriptional regulatory mechanisms were defined: IRE1β selectively degrades MTP mRNA in intestine to limit chylomicron production, and FoxO1 directly activates MTP transcription in liver, with insulin suppressing MTP via FoxO1 inhibition.

    Evidence Ire1b−/− mice and enterocyte studies; FoxO1 transgenic mice, hepatic FoxO1 RNAi, promoter binding assays

    PMID:18460335 PMID:18497885

    Open questions at the time
    • Whether IRE1β acts via RIDD or another decay mechanism not fully resolved
    • FoxO1 binding site in MTP promoter fine-mapping not complete
  9. 2010 High

    A CLOCK–SHP circadian axis was shown to impose diurnal oscillation on MTP expression and plasma triglycerides, revealing a molecular basis for the circadian variation in VLDL production.

    Evidence Clock mutant and Shp−/− mouse models, serum shock oscillation assays, siRNA, MTP promoter analysis

    PMID:20674862

    Open questions at the time
    • Relative contribution of intestinal vs. hepatic circadian MTP regulation not dissected
    • Whether other clock output genes synergize with SHP on MTP unknown
  10. 2012 High

    The IRE1α–XBP1s–PDI axis was shown to regulate hepatic MTP activity by controlling PDI abundance, linking ER stress signaling to VLDL lipidation capacity independently of apoB synthesis.

    Evidence Hepatocyte-specific Ire1α knockout mice, VLDL lipid composition, MTP activity and PDI expression measurement

    PMID:23040069

    Open questions at the time
    • Whether XBP1s regulates PDI transcriptionally or post-transcriptionally not fully defined
    • Interaction between IRE1α and IRE1β pathways in dual-expressing tissues not explored
  11. 2013 High

    miR-30c was identified as a post-transcriptional repressor of MTP through direct 3ʹ UTR targeting; hepatic miR-30c overexpression reduced hyperlipidemia and atherosclerosis in vivo, establishing miR-30c as a physiological brake on MTP-dependent lipoprotein production.

    Evidence 3ʹ UTR reporter assay, hepatic miR-30c overexpression and anti-miR in Apoe−/− mice, MTP activity and atherosclerosis quantification

    PMID:23749231

    Open questions at the time
    • Endogenous signals that regulate miR-30c expression in liver not identified
    • Off-target effects of miR-30c on lipid synthesis pathway confound interpretation of MTP-specific contribution
  12. 2020 High

    PRAP1 was identified as a novel ER-localized lipid-binding partner that forms a ternary complex with TG and MTTP to facilitate lipid transfer; disruption of this complex in vivo reduced lipid absorption and protected against diet-induced obesity.

    Evidence Co-localization, direct TG-binding assay, MTTP lipid transfer assay, E85V mutagenesis, PRAP1-KO and E85V knock-in mice

    PMID:33168624

    Open questions at the time
    • Stoichiometry and structural basis of the MTTP–PRAP1–TG ternary complex unknown
    • Whether PRAP1 modulates CD1d lipidation by MTP not tested
  13. 2022 Medium

    An exosomal route for MTTP was discovered in which adipocyte-derived exosomal MTTP complexes with PRAP1 in colorectal cancer cells to suppress ferroptosis via GPX4/xCT upregulation, implicating MTP in chemoresistance independent of canonical lipoprotein assembly.

    Evidence Exosome isolation, Co-IP of MTTP/PRAP1, GPX4/xCT/ZEB1 expression, lipid ROS measurement, CRC organoids and obese mouse tumor model with MTP inhibitor

    PMID:35978266

    Open questions at the time
    • Mechanism by which MTTP/PRAP1 regulates ZEB1/GPX4 transcription not defined
    • Independent replication by another group needed
    • Whether exosomal MTTP retains lipid transfer activity not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of the MTTP–PDI heterodimer with bound lipid substrate is lacking, and the precise mechanism by which MTTP transfers lipid to the growing apoB polypeptide in the ER lumen remains unresolved at the molecular level.
  • No crystal or cryo-EM structure of MTTP–PDI complex
  • Mechanism of coupling between apoB translocation and MTP-mediated lipid loading not defined
  • Relative contribution of neutral lipid vs. phospholipid transfer to initial apoB lipidation unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 5 GO:0140104 molecular carrier activity 4
Localization
GO:0005783 endoplasmic reticulum 3
Pathway
R-HSA-1430728 Metabolism 7 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-162582 Signal Transduction 3 R-HSA-8963743 Digestion and absorption 2 R-HSA-168256 Immune System 1 R-HSA-9909396 Circadian clock 1
Partners
APOBCD1DFOXO1HNF1AHNF4ANR0B2P4HBPRAP1
Complex memberships
MTP heterodimer (MTTP large subunit + PDI/P4HB)MTTP–PRAP1–TG ternary complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 MTP activity and its 88-kDa large subunit are absent in intestinal biopsy samples from abetalipoproteinemia patients, establishing that a defect in MTP is the molecular basis of abetalipoproteinemia and that MTP is required for lipoprotein assembly. MTP activity assay and immunodetection in intestinal biopsies from ABL patients vs. controls Science High 1439810
1993 cDNA cloning of the large subunit of MTP revealed homozygous frameshift and nonsense mutations in two abetalipoproteinemic subjects, proving that defects in the MTP large-subunit gene are the proximal cause of ABL. The predicted amino acid sequence shows extensive homology to vitellogenin, which contains a large lipid-storage cavity. cDNA cloning, sequencing, and comparative genomic analysis; cell expression in COS-1 cells Nature High 8361539
1993 The human MTP gene was cloned and localized to chromosome 4q22-24. The C-terminal portion of MTP is necessary for triglyceride-transfer activity: deletion of 20 amino acids from the carboxyl terminus or a missense mutation of Cys878→Ser both abolished activity. Homozygous splice-disrupting mutations were identified in ABL patients. cDNA cloning, site-directed mutagenesis, expression in COS-1 cells with activity assay, patient mutation identification Human molecular genetics High 8111381
1994 MTP gene promoter analysis showed cell-type-specific expression restricted to liver and intestinal cells, mediated by HNF-1 and HNF-4 binding elements in the -123 to -85 bp region. The promoter contains a modified sterol response element and a negative insulin response element; cholesterol positively and insulin negatively regulate MTP promoter activity. Promoter cloning, deletion analysis, transient transfection/luciferase reporter assay in liver, intestinal, and epithelial cell lines The Journal of biological chemistry High 7961826
1995 All eight individuals in an ABL cohort carry mutations in the MTP gene on both alleles, each predicted to encode a truncated MTP protein, confirming MTP gene defects as the predominant cause of hereditary ABL and that an intact carboxyl terminus is required for triglyceride-transfer activity. MTP gene characterization, mutation screening across patient cohort, expression of engineered MTP forms in COS-1 cells American journal of human genetics High 8533758
1996 The MTP inhibitor BMS-200150 directly binds bovine MTP (Kd ~1.3 µM) and inhibits its triglyceride transfer activity (IC50 ~0.6 µM). Addition to HepG2 cells inhibits apoB secretion in a concentration-dependent manner, establishing that MTP-mediated neutral lipid transfer is mechanistically required for assembly of apoB-containing lipoproteins. In vitro MTP lipid transfer assay, binding assay, HepG2 cell apoB secretion assay with pharmacological inhibitor Proceedings of the National Academy of Sciences of the United States of America High 8876250
1997 MTP is a heterodimer composed of the unique large (~88 kDa) subunit and protein disulfide isomerase (PDI); this complex catalyzes transport of triglyceride, cholesteryl ester, and phospholipid between phospholipid surfaces and is located in the lumen of the ER in liver and intestine. Biochemical purification, activity assays, subunit characterization Biochimica et biophysica acta High 9106493
1997 MTP plays a key early role in lipoprotein assembly by transferring lipid to nascent apoB as it enters the ER lumen; MTP controls the number of apoB lipoprotein particles secreted but does not primarily determine the lipid composition of the particles. Heterologous expression systems and MTP inhibitor studies in hepatoma cell lines Current opinion in lipidology Medium 9211060
2000 Six novel MTP gene mutations (two nonsense, two missense, one frameshift, one splice-donor) were identified in Canadian ABL subjects, demonstrating wide genotypic heterogeneity and showing that clinical severity correlates with age at diagnosis and vitamin treatment onset rather than mutation type or position. MTP gene sequencing in patient cohort, genotype-phenotype correlation Human mutation Medium 10679949
2003 Insulin suppresses MTP gene transcription in HepG2 cells through the MAPKerk cascade (not PI3K), while MAPKp38 activity counterbalances this suppression, identifying the specific signal transduction pathways by which insulin regulates hepatic MTP expression and thereby VLDL production. Chemical inhibitors of signaling cascades, constitutively active and dominant-negative kinase constructs, MTP promoter-luciferase reporter assays Diabetes High 12716735
2004 The MTP gene promoter contains functional HNF-4α responsive elements, and HNF-4α regulates MTP expression directly and indirectly through HNF-1. Bile acid (CDCA) activates FXR, which induces small heterodimer partner (SHP), which suppresses HNF-4α activity, thereby reducing MTP mRNA, MTP protein, and apoB secretion. Chromatin immunoprecipitation (ChIP), siRNA knockdown, dominant-negative HNF-4α overexpression, MTP promoter-luciferase reporter assays in HepG2 cells The Journal of biological chemistry High 15337761
2005 MTP is expressed in retinal pigment epithelium (RPE) and retinal ganglion cells, and RPE cells (ARPE-19) synthesize and secrete neutral lipids (esterified cholesterol and triglyceride), implicating MTP-dependent lipoprotein assembly as a constitutive retinal function that may contribute to Bruch's membrane lipid deposition in age-related maculopathy. RT-PCR, immunodetection of MTP in retinal tissue and ARPE-19 cells; radiolabeled lipid secretion assay Journal of lipid research Medium 15654125
2005 MTP has two additional functional roles beyond VLDL/chylomicron assembly: (1) production of small apoB-containing lipoprotein particles in cardiac myocytes, and (2) lipidation of CD1d (an MHC class I-related molecule) that presents glycolipid antigens to natural killer T (NKT) cells. Review synthesizing experimental data including lipid transfer assays and CD1d lipidation studies Current topics in medicinal chemistry Medium 15857311
2007 MTP regulated by an alternative promoter is expressed as a novel splice variant (MTPv1) in non-apoB-secreting tissues including thymocytes and antigen-presenting cells. MTPv1 efficiently transfers phosphatidylethanolamine to CD1d in vitro. MTP inhibition in fetal thymic organ culture blocks NKT cell development and CD1d tetramer-positive cell generation, without affecting surface CD1d levels, establishing MTP's role in lipid loading of CD1d for NKT cell selection. PCR, Northern analysis, Edman degradation sequencing, in vitro phospholipid transfer to CD1d, fetal thymic organ culture with MTP antagonists, NKT cell quantification by tetramer staining The Journal of experimental medicine High 17312007
2008 IRE1β (an ER stress sensor isoform expressed in intestine) selectively degrades MTP mRNA post-transcriptionally, thereby suppressing intestinal MTP expression and chylomicron production. Ire1b-/- mice develop hyperlipidemia due to increased intestinal MTP expression and chylomicron secretion; IRE1α does not regulate MTP mRNA. Ire1b-/- mouse phenotyping, primary enterocyte isolation, siRNA knockdown of IRE1β in cell culture, measurement of MTP mRNA stability and chylomicron secretion Cell metabolism High 18460335
2008 FoxO1 directly binds to and stimulates the MTP promoter, inducing MTP expression and VLDL production in a hepatic context. Constitutively active FoxO1 mice show enhanced MTP expression and hypertriglyceridemia; RNAi silencing of hepatic FoxO1 reduces MTP and VLDL production. Insulin suppresses MTP through inhibition of FoxO1. Promoter binding assays, FoxO1 transgenic mice, RNAi-mediated hepatic FoxO1 knockdown in adult mice, VLDL production and MTP activity measurements The Journal of clinical investigation High 18497885
2010 CLOCK regulates diurnal MTP expression and plasma triglyceride cycling through the small heterodimer partner (SHP/NR0B2). CLOCK binds the SHP E-box to upregulate SHP, which then suppresses MTP by binding HNF-4α/LRH-1 at the MTP promoter. Clock(mt/mt) mice show sustained hypertriglyceridemia and high MTP expression; Shp-/- mice lose diurnal variation in both MTP and triglycerides; SHP expression corrects hypertriglyceridemia in Clock(mt/mt) mice. Clock mutant and Shp-/- mouse models, serum shock oscillation assays, siRNA knockdown, MTP promoter analysis, plasma triglyceride and MTP expression measurements Cell metabolism High 20674862
2012 The IRE1α–XBP1s arm of the unfolded protein response regulates VLDL assembly via MTP. Hepatocyte-specific Ire1α deletion reduces lipid partitioning into the ER lumen and impairs TG-rich VLDL assembly without affecting TG synthesis or apoB synthesis/secretion. The defect is due to reduced MTP activity caused by decreased PDI expression; thus the IRE1α–XBP1s–PDI axis controls MTP activity. Hepatocyte-specific Ire1α knockout mice, VLDL lipid composition analysis, MTP activity assay, PDI expression measurement Cell metabolism High 23040069
2012 NR2F1 represses synergistic activation of the MTP promoter by HNF-4α/HNF-1α by binding to a DR1 element and recruiting nuclear receptor corepressor 1 (NCoR1), without affecting individual activities of HNF-4α or HNF-1α alone. This defines a mechanism for MTP repression in undifferentiated intestinal cells. MTP promoter-luciferase reporter assays, electrophoretic mobility shift assay (EMSA), co-transfection of HNF-4α, HNF-1α, NR2F1, and NCoR1 Journal of lipid research Medium 22357705
2012 Two novel MTTP mutations in an atypical ABL patient (missense p.Leu435His and intronic deletion c.619-5_619-2del) were characterized: the missense mutant showed negligible MTP activity in COS-1 cells; the intronic deletion caused incomplete splicing defect retaining 26% normal splicing, explaining the milder atypical phenotype through residual MTP activity. MTP activity assay in COS-1 cells (missense mutant expression), minigene splicing reporter assay in HeLa cells (intronic deletion) Journal of lipid research Medium 22236406
2013 MicroRNA-30c (miR-30c) interacts with the 3' UTR of MTP mRNA and induces its degradation, reducing MTP activity and apoB secretion. miR-30c also independently reduces lipid synthesis. Hepatic overexpression of miR-30c in mice reduced hyperlipidemia and atherosclerosis; anti-miR-30c increased hyperlipidemia and atherosclerosis. 3' UTR reporter assay, hepatic miR-30c overexpression and anti-miR knockdown in mice, MTP activity assay, VLDL/apoB secretion measurements, atherosclerosis quantification in Apoe-/- mice Nature medicine High 23749231
2014 Intestinal-specific MTP deletion increases intestinal triglyceride and cholesterol levels and reduces their transport with chylomicrons. Combined intestinal MTP and global ACAT2 deficiency reduces cholesterol secretion with both chylomicrons and HDLs, demonstrating that MTP is required for chylomicron assembly and that free cholesterol accumulated during ACAT2 deficiency is unavailable for HDL secretion when MTP is absent. ACAT2 deficiency increases hepatic MTP activity to compensate for hepatosteatosis. Intestine-specific MTP knockout mice, global ACAT2 knockout mice, double knockout mice; cholesterol absorption assay, lipoprotein fractionation, MTP activity assay Journal of lipid research High 25030663
2020 PRAP1 is a novel lipid-binding protein that colocalizes with MTTP in the ER and directly binds triglyceride. PRAP1 facilitates MTTP-mediated lipid transfer by forming a ternary complex with TG and MTTP; mutation E85V disrupts ternary complex formation and abolishes PRAP1's ability to facilitate MTTP-mediated apoB-containing lipoprotein assembly and secretion. PRAP1-deficient and E85V knock-in mice show reduced lipid absorption and resistance to diet-induced obesity and hepatosteatosis. Co-localization studies, direct TG-binding assay, MTTP-mediated lipid transfer assay, E85V mutagenesis, apoB lipoprotein secretion assay, PRAP1-KO and E85V knock-in mouse models on chow and HFD The Journal of biological chemistry High 33168624
2022 Adipocyte-derived exosomal MTTP is transferred to colorectal cancer (CRC) cells where it forms a complex with PRAP1; the MTTP/PRAP1 complex inhibits ZEB1 expression and upregulates GPX4 and xCT, decreasing polyunsaturated fatty acid ratio and lipid ROS levels, thereby suppressing ferroptosis and promoting chemoresistance to oxaliplatin. MTTP inhibition restored oxaliplatin sensitivity in CRC organoids and obese mouse tumor models. Exosome isolation and characterization, Co-IP of MTTP/PRAP1 complex, GPX4/xCT/ZEB1 expression analysis, lipid ROS measurement, CRC organoids, obese mouse tumor implantation model with MTP inhibitor treatment Advanced science Medium 35978266

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nature medicine 2866 8616716
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
2016 An improved smaller biotin ligase for BioID proximity labeling. Molecular biology of the cell 665 26912792
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1990 Acute leukaemia in bcr/abl transgenic mice. Nature 610 2179728
1992 Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia. Science (New York, N.Y.) 609 1439810
1999 Interaction of c-Abl and p73alpha and their collaboration to induce apoptosis. Nature 496 10391250
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
1990 Induction of a chronic myelogenous leukemia-like syndrome in mice with v-abl and BCR/ABL. Proceedings of the National Academy of Sciences of the United States of America 461 2204061
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2004 Regulation of the c-Abl and Bcr-Abl tyrosine kinases. Nature reviews. Molecular cell biology 392 14708008
2003 A myristoyl/phosphotyrosine switch regulates c-Abl. Cell 378 12654250
1992 Dominant negative MYC blocks transformation by ABL oncogenes. Cell 376 1525828
1993 Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia. Nature 367 8361539
2006 AMN107 (nilotinib): a novel and selective inhibitor of BCR-ABL. British journal of cancer 354 16721371
2013 Role of ABL family kinases in cancer: from leukaemia to solid tumours. Nature reviews. Cancer 351 23842646
2007 Sequential ABL kinase inhibitor therapy selects for compound drug-resistant BCR-ABL mutations with altered oncogenic potency. The Journal of clinical investigation 318 17710227
1999 In vivo eradication of human BCR/ABL-positive leukemia cells with an ABL kinase inhibitor. Journal of the National Cancer Institute 288 9923858
1986 Alternative 5' exons in c-abl mRNA. Cell 281 3512096
2002 Critical role for Gab2 in transformation by BCR/ABL. Cancer cell 276 12124177
1997 Microsomal triglyceride transfer protein. Biochimica et biophysica acta 268 9106493
2013 MicroRNA-30c reduces hyperlipidemia and atherosclerosis in mice by decreasing lipid synthesis and lipoprotein secretion. Nature medicine 254 23749231
2000 Regulation of cell death by the Abl tyrosine kinase. Oncogene 230 11114745
2008 FoxO1 mediates insulin-dependent regulation of hepatic VLDL production in mice. The Journal of clinical investigation 228 18497885
2000 Bcr/Abl activates transcription of the Bcl-X gene through STAT5. Blood 217 10979976
1993 Abetalipoproteinemia is caused by defects of the gene encoding the 97 kDa subunit of a microsomal triglyceride transfer protein. Human molecular genetics 217 8111381
2011 Molecular pathways: BCR-ABL. Clinical cancer research : an official journal of the American Association for Cancer Research 199 22156549
2022 Adipocyte-Derived Exosomal MTTP Suppresses Ferroptosis and Promotes Chemoresistance in Colorectal Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 197 35978266
2002 Autoinhibition of c-Abl. Cell 195 11832214
2004 Polymorphisms of microsomal triglyceride transfer protein gene and manganese superoxide dismutase gene in non-alcoholic steatohepatitis. Journal of hepatology 191 15094225
2012 IRE1α-XBP1s induces PDI expression to increase MTP activity for hepatic VLDL assembly and lipid homeostasis. Cell metabolism 188 23040069
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
2004 Mechanisms and implications of imatinib resistance mutations in BCR-ABL. Current opinion in hematology 163 14676625
2003 Molecular mechanisms of transformation by the BCR-ABL oncogene. Seminars in hematology 160 12783368
2001 STI571: targeting BCR-ABL as therapy for CML. The oncologist 158 11423669
2014 The capable ABL: what is its biological function? Molecular and cellular biology 152 24421390
1987 The CML-specific P210 bcr/abl protein, unlike v-abl, does not transform NIH/3T3 fibroblasts. Science (New York, N.Y.) 150 2440107
2010 Diurnal regulation of MTP and plasma triglyceride by CLOCK is mediated by SHP. Cell metabolism 145 20674862
1996 An inhibitor of the microsomal triglyceride transfer protein inhibits apoB secretion from HepG2 cells. Proceedings of the National Academy of Sciences of the United States of America 144 8876250
2004 Bile acid reduces the secretion of very low density lipoprotein by repressing microsomal triglyceride transfer protein gene expression mediated by hepatocyte nuclear factor-4. The Journal of biological chemistry 142 15337761
2000 Mice deficient in Abl are osteoporotic and have defects in osteoblast maturation. Nature genetics 125 10700189
1995 Mutations of the microsomal triglyceride-transfer-protein gene in abetalipoproteinemia. American journal of human genetics 125 8533758
2013 Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins. Proceedings of the National Academy of Sciences of the United States of America 121 23382219
1988 The viral and cellular forms of the Abelson (abl) oncogene. Advances in virus research 121 2852893
2003 Autoinhibition of Bcr-Abl through its SH3 domain. Molecular cell 118 12887890
2000 c-Abl: activation and nuclear targets. Cell death and differentiation 118 10713716
2014 Homozygous MTTP and APOB mutations may lead to hepatic steatosis and fibrosis despite metabolic differences in congenital hypocholesterolemia. Journal of hepatology 116 24842304
1997 BCR-ABL gene variants. Bailliere's clinical haematology 116 9376660
2003 Haplotype-based identification of a microsomal transfer protein marker associated with the human lifespan. Proceedings of the National Academy of Sciences of the United States of America 114 14615589
2007 Reliance of host cholesterol metabolic pathways for the life cycle of hepatitis C virus. PLoS pathogens 113 17784784
2000 JAK-STAT signaling activated by Abl oncogenes. Oncogene 112 10851051
2011 Targeting the SH2-kinase interface in Bcr-Abl inhibits leukemogenesis. Cell 111 22000011
2008 IRE1beta inhibits chylomicron production by selectively degrading MTP mRNA. Cell metabolism 108 18460335
1994 Transcriptional regulation of human and hamster microsomal triglyceride transfer protein genes. Cell type-specific expression and response to metabolic regulators. The Journal of biological chemistry 107 7961826
2006 Messenger RNA levels of genes involved in dysregulation of postprandial lipoproteins in type 2 diabetes: the role of Niemann-Pick C1-like 1, ATP-binding cassette, transporters G5 and G8, and of microsomal triglyceride transfer protein. Diabetologia 104 16518588
2018 Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei. Molecular & cellular proteomics : MCP 101 30021884
2016 Multifunctional Abl kinases in health and disease. Journal of cell science 101 26729027
2013 Structure and dynamic regulation of Abl kinases. The Journal of biological chemistry 95 23316053
2006 Activity of dual SRC-ABL inhibitors highlights the role of BCR/ABL kinase dynamics in drug resistance. Proceedings of the National Academy of Sciences of the United States of America 95 16754879
2005 Retina expresses microsomal triglyceride transfer protein: implications for age-related maculopathy. Journal of lipid research 95 15654125
2012 The ins and outs of bcr-abl inhibition. Genes & cancer 93 23226582
2007 Polymorphism in microsomal triglyceride transfer protein: a link between liver disease and atherogenic postprandial lipid profile in NASH? Hepatology (Baltimore, Md.) 92 17464986
2004 Human placenta secretes apolipoprotein B-100-containing lipoproteins. The Journal of biological chemistry 91 15504742
2003 Regulation of microsomal triglyceride transfer protein gene by insulin in HepG2 cells: roles of MAPKerk and MAPKp38. Diabetes 91 12716735
2004 Requirement for Abl kinases in T cell receptor signaling. Current biology : CB 87 15268851
2011 Viral genotype-specific role of PNPLA3, PPARG, MTTP, and IL28B in hepatitis C virus-associated steatosis. Journal of hepatology 86 21236304
2006 A common phosphotyrosine signature for the Bcr-Abl kinase. Blood 83 16497976
2005 No association between microsomal triglyceride transfer protein (MTP) haplotype and longevity in humans. Proceedings of the National Academy of Sciences of the United States of America 83 15911777
1997 Recent advances in elucidating the role of the microsomal triglyceride transfer protein in apolipoprotein B lipoprotein assembly. Current opinion in lipidology 80 9211060
2008 BCR/ABL inhibits mismatch repair to protect from apoptosis and induce point mutations. Cancer research 74 18413724
1997 BCR/ABL-negative chronic myeloid leukemia with ETV6/ABL fusion. Genes, chromosomes & cancer 74 9365838
1988 Localization of gelsolin proximal to ABL on chromosome 9. American journal of human genetics 74 2831714
2001 Multiple signaling interactions of Abl and Arg kinases with the EphB2 receptor. Oncogene 70 11494128
1996 Nuclear tyrosine kinases: from Abl to WEE1. Current opinion in cell biology 68 8791414
1991 Drosophila abl and genetic redundancy in signal transduction. Trends in genetics : TIG 67 1820686
1997 Interactions of CBL with BCR-ABL and CRKL in BCR-ABL-transformed myeloid cells. The Journal of biological chemistry 63 9195915
2010 Bag1 directly routes immature BCR-ABL for proteasomal degradation. Blood 62 20675402
2004 Controlling Abl: auto-inhibition and co-inhibition? Nature cell biology 62 14704671
2004 c-Abl phosphorylates Dok1 to promote filopodia during cell spreading. The Journal of cell biology 62 15148308
2001 Mechanisms of transformation by the BCR/ABL oncogene. International journal of hematology 60 11345193
1989 Nucleotide sequence analysis of human abl and bcr-abl cDNAs. Oncogene 59 2687768
2005 Structural basis for the cytoskeletal association of Bcr-Abl/c-Abl. Molecular cell 58 16109371
2007 MTP regulated by an alternate promoter is essential for NKT cell development. The Journal of experimental medicine 55 17312007
2009 Abl tyrosine kinases in T-cell signaling. Immunological reviews 54 19290927
2008 c-Abl phosphorylates Hdmx and regulates its interaction with p53. The Journal of biological chemistry 54 19075013
2003 Caspase-dependent cleavage of c-Abl contributes to apoptosis. Molecular and cellular biology 54 12665579
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