Targeted disruption of the idol gene alters cellular regulation of the low-density lipoprotein receptor by sterols and liver x receptor agonists.


:Previously, we identified the E3 ubiquitin ligase Idol (inducible degrader of the low-density lipoprotein [LDL] receptor [LDLR]) as a posttranscriptional regulator of the LDLR pathway. Idol stimulates LDLR degradation through ubiquitination of its C-terminal domain, thereby limiting cholesterol uptake. Here we report the generation and characterization of mouse embryonic stem cells homozygous for a null mutation in the Idol gene. Cells lacking Idol exhibit markedly elevated levels of the LDLR protein and increased rates of LDL uptake. Furthermore, despite an intact sterol responsive element-binding protein (SREBP) pathway, Idol-null cells exhibit an altered response to multiple regulators of sterol metabolism, including serum, oxysterols, and synthetic liver X receptor (LXR) agonists. The ability of oxysterols and lipoprotein-containing serum to suppress LDLR protein levels is reduced, and the time course of suppression is delayed, in cells lacking Idol. LXR ligands have no effect on LDLR levels in Idol-null cells, indicating that Idol is required for LXR-dependent inhibition of the LDLR pathway. In line with these results, the half-life of the LDLR protein is prolonged in the absence of Idol. Finally, the ability of statins and PCSK9 to alter LDLR levels is independent of, and additive with, the LXR-Idol pathway. These results demonstrate that the LXR-Idol pathway is an important contributor to feedback inhibition of the LDLR by sterols and a biological determinant of cellular LDL uptake.


Mol Cell Biol


Scotti E,Hong C,Yoshinaga Y,Tu Y,Hu Y,Zelcer N,Boyadjian R,de Jong PJ,Young SG,Fong LG,Tontonoz P




Has Abstract


2011-05-01 00:00:00














  • Mutational and kinetic analyses of the GTPase-activating protein (GAP)-p21 interaction: the C-terminal domain of GAP is not sufficient for full activity.

    abstract::The GTPase-activating protein (GAP) stimulates the GTPase reaction of p21 by 5 orders of magnitude such that the kcat of the reaction is increased to 19 s-1. Mutations of residues in loop L1 (Gly-12 and Gly-13), in loop L2 (Thr-35 and Asp-38), and in loop L4 (Gln-61 and Glu-63) influence the reaction in different ways...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Gideon P,John J,Frech M,Lautwein A,Clark R,Scheffler JE,Wittinghofer A

    更新日期:1992-05-01 00:00:00

  • Multiple pathways promote short-sequence recombination in Saccharomyces cerevisiae.

    abstract::In the budding yeast Saccharomyces cerevisiae, null alleles of several DNA repair and recombination genes confer defects in recombination that grow more severe with decreasing sequence length, indicating that they are required for short-sequence recombination (SSR). RAD1 and RAD10, which encode the subunits of the str...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Manthey GM,Bailis AM

    更新日期:2002-08-01 00:00:00

  • The protein encoded by a growth arrest-specific gene (gas6) is a new member of the vitamin K-dependent proteins related to protein S, a negative coregulator in the blood coagulation cascade.

    abstract::A set of growth arrest-specific genes (gas) whose expression is negatively regulated after serum induction has previously been described (C. Schneider, R. M. King, and L. Philipson, Cell 54:787-793, 1988). The detailed analysis of one of them, gas6, is reported here, gas6 mRNA (2.6 kb) is abundantly expressed in serum...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Manfioletti G,Brancolini C,Avanzi G,Schneider C

    更新日期:1993-08-01 00:00:00

  • GATA and Ets cis-acting sequences mediate megakaryocyte-specific expression.

    abstract::The human glycoprotein IIB (GPIIB) gene is expressed only in megakaryocytes, and its promoter displays cell type specificity. We show that this specificity involved two cis-acting sequences. The first one, located at -55, contains a GATA binding site. Point mutations that abolish protein binding on this site decrease ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Lemarchandel V,Ghysdael J,Mignotte V,Rahuel C,Roméo PH

    更新日期:1993-01-01 00:00:00

  • Cyclin-dependent kinase suppression by WEE1 kinase protects the genome through control of replication initiation and nucleotide consumption.

    abstract::Activation of oncogenes or inhibition of WEE1 kinase deregulates cyclin-dependent kinase (CDK) activity and leads to replication stress; however, the underlying mechanism is not understood. We now show that elevation of CDK activity by inhibition of WEE1 kinase rapidly increases initiation of replication. This leads t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Beck H,Nähse-Kumpf V,Larsen MS,O'Hanlon KA,Patzke S,Holmberg C,Mejlvang J,Groth A,Nielsen O,Syljuåsen RG,Sørensen CS

    更新日期:2012-10-01 00:00:00

  • Forkhead transcription factor FoxM1 regulates mitotic entry and prevents spindle defects in cerebellar granule neuron precursors.

    abstract::The forkhead transcription factor FoxM1 has been reported to regulate, variously, proliferation and/or spindle formation during the G2/M transition of the cell cycle. Here we define specific functions of FoxM1 during brain development by the investigation of FoxM1 loss-of-function mutations in the context of Sonic hed...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Schüller U,Zhao Q,Godinho SA,Heine VM,Medema RH,Pellman D,Rowitch DH

    更新日期:2007-12-01 00:00:00

  • Numb proteins specify asymmetric cell fates via an endocytosis- and proteasome-independent pathway.

    abstract::Numb proteins are evolutionarily conserved signaling molecules that make the daughter cells different after asymmetric divisions by segregating to only one daughter. They contain distinct binding motifs for alpha-adaptin (alpha-Ada) and proteins with Eps15 homology (EH) domains, which regulate endocytosis, and for E3 ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Tang H,Rompani SB,Atkins JB,Zhou Y,Osterwalder T,Zhong W

    更新日期:2005-04-01 00:00:00

  • A severely defective TATA-binding protein-TFIIB interaction does not preclude transcriptional activation in vivo.

    abstract::In yeast cells, mutations in the TATA-binding protein (TBP) that disrupt the interaction with the TATA element or with TFIIA can selectively impair the response to acidic activator proteins. We analyzed the transcriptional properties of TBP derivatives in which residues that directly interact with TFIIB were replaced ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Lee M,Struhl K

    更新日期:1997-03-01 00:00:00

  • RNA polymerase II accumulation in the promoter-proximal region of the dihydrofolate reductase and gamma-actin genes.

    abstract::The carboxyl-terminal domain (CTD) of RNA polymerase II (Pol II) can be phosphorylated at serine 2 (Ser-2) and serine 5 (Ser-5) of the CTD heptad repeat YSPTSPS, and this phosphorylation is important in coupling transcription to RNA processing, including 5' capping, splicing, and polyadenylation. The mammalian endogen...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Cheng C,Sharp PA

    更新日期:2003-03-01 00:00:00

  • Age-related macular degeneration-associated silent polymorphisms in HtrA1 impair its ability to antagonize insulin-like growth factor 1.

    abstract::Synonymous single nucleotide polymorphisms (SNPs) within a transcript's coding region produce no change in the amino acid sequence of the protein product and are therefore intuitively assumed to have a neutral effect on protein function. We report that two common variants of high-temperature requirement A1 (HTRA1) tha...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Jacobo SM,Deangelis MM,Kim IK,Kazlauskas A

    更新日期:2013-05-01 00:00:00

  • Six mouse alpha-tubulin mRNAs encode five distinct isotypes: testis-specific expression of two sister genes.

    abstract::Five mouse alpha-tubulin isotypes are described, each distinguished by the presence of unique amino acid substitutions within the coding region. Most, though not all of these isotype-specific amino acids, are clustered at the carboxy terminus. One of the alpha-tubulin isotypes described is expressed exclusively in tes...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Villasante A,Wang D,Dobner P,Dolph P,Lewis SA,Cowan NJ

    更新日期:1986-07-01 00:00:00

  • Cloning and expression of two human genes encoding calcium-binding proteins that are regulated during myeloid differentiation.

    abstract::The cellular mechanisms involved in chronic inflammatory processes are poorly understood. This is especially true for the role of macrophages, which figure prominently in the inflammatory response. Two proteins, MRP8 and MRP14, which are expressed in infiltrate macrophages during inflammatory reactions but not in norm...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Lagasse E,Clerc RG

    更新日期:1988-06-01 00:00:00

  • Germ line transcripts are processed by a Dicer-like protein that is essential for developmentally programmed genome rearrangements of Tetrahymena thermophila.

    abstract::Abundant approximately 28-nucleotide RNAs that are thought to direct histone H3 lysine 9 (H3K9) methylation and promote the elimination of nearly 15 Mbp of DNA from the developing somatic genome are generated during Tetrahymena thermophila conjugation. To identify the protein(s) that generates these small RNAs, we stu...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Malone CD,Anderson AM,Motl JA,Rexer CH,Chalker DL

    更新日期:2005-10-01 00:00:00

  • Tissue localization of Drosophila melanogaster ras transcripts during development.

    abstract::Three ras homologs have been identified in Drosophila melanogaster. Here we describe the tissue distribution of their transcripts as analyzed by in situ hybridization. The RNAs of the three genes show a similar distribution at every developmental stage examined. In embryos, the transcripts are uniformly distributed. I...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Segal D,Shilo BZ

    更新日期:1986-06-01 00:00:00

  • The Drosophila Hrb98DE locus encodes four protein isoforms homologous to the A1 protein of mammalian heterogeneous nuclear ribonucleoprotein complexes.

    abstract::The Drosophila Hrb98DE locus encodes proteins that are highly homologous to the mammalian A1 protein, a major component of heterogeneous nuclear ribonucleoprotein (RNP) particles. The Hrb98DE locus is transcribed throughout development, with the highest transcript levels found in ovaries, early embryos, and pupae. Eig...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Haynes SR,Raychaudhuri G,Beyer AL

    更新日期:1990-01-01 00:00:00

  • Domains of human c-myc protein required for autosuppression and cooperation with ras oncogenes are overlapping.

    abstract::Amino acids 106 to 143 and 354 to 433 of the human c-myc protein (439 amino acids) were shown to be required for the protein to suppress c-myc gene transcription and were found to exactly overlap with those necessary for c-myc to cooperate with ras oncogenes in the transformation of rat embryo fibroblasts. The essenti...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Penn LJ,Brooks MW,Laufer EM,Littlewood TD,Morgenstern JP,Evan GI,Lee WM,Land H

    更新日期:1990-09-01 00:00:00

  • Induction of yeast histone genes by stimulation of stationary-phase cells.

    abstract::In the cell cycle of the budding yeast Saccharomyces cerevisiae, expression of the histone genes H2A and H2B of the TRT1 and TRT2 loci is regulated by the performance of "start," the step that also regulates the cell cycle. Here we show that histone production is also subject to an additional form of regulation that i...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Drebot MA,Veinot-Drebot LM,Singer RA,Johnston GC

    更新日期:1990-12-01 00:00:00

  • Alternative mechanisms by which mediator subunit MED1/TRAP220 regulates peroxisome proliferator-activated receptor gamma-stimulated adipogenesis and target gene expression.

    abstract::Mediator is a general coactivator complex connecting transcription activators and RNA polymerase II. Recent work has shown that the nuclear receptor-interacting MED1/TRAP220 subunit of Mediator is required for peroxisome proliferator-activated receptor gamma (PPARgamma)-stimulated adipogenesis of mouse embryonic fibro...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Ge K,Cho YW,Guo H,Hong TB,Guermah M,Ito M,Yu H,Kalkum M,Roeder RG

    更新日期:2008-02-01 00:00:00

  • H5 gene specific trans-activation by nuclear extracts from avian erythroid cells.

    abstract::Nuclear extracts from chicken erythroid cells selectively stimulate transcription of the chicken histone H5 gene (and not of other chicken histone genes) after coinjection into frog oocytes. This effect is shown to involve an enhancerlike activity, and a region of the H5 gene sufficient to mediate trans-activation is ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Wigley PL,Wells JR

    更新日期:1987-10-01 00:00:00

  • Synergistic interactions between heterologous upstream activation elements and specific TATA sequences in a muscle-specific promoter.

    abstract::Previous investigations have defined three upstream activation elements--CCAC, A/T, and TATA sequences--necessary for muscle-specific transcription of the myoglobin gene. In the present study, we demonstrate that these three sequences elements, prepared as synthetic oligonucleotide cassettes, function synergistically ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Grayson J,Williams RS,Yu YT,Bassel-Duby R

    更新日期:1995-04-01 00:00:00

  • Ionophore-resistant mutants of Toxoplasma gondii reveal host cell permeabilization as an early event in egress.

    abstract::Toxoplasma gondii is an obligate intracellular pathogen within the phylum Apicomplexa. Invasion and egress by this protozoan parasite are rapid events that are dependent upon parasite motility and appear to be directed by fluctuations in intracellular [Ca(2+)]. Treatment of infected host cells with the calcium ionopho...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Black MW,Arrizabalaga G,Boothroyd JC

    更新日期:2000-12-01 00:00:00

  • Complementation of growth factor receptor-dependent mitogenic signaling by a truncated type I phosphatidylinositol 4-phosphate 5-kinase.

    abstract::Substitution of phenylalanine for tyrosine at codon 809 (Y809F) of the human colony-stimulating factor 1 (CSF-1) receptor (CSF-1R) impairs ligand-stimulated tyrosine kinase activity, prevents induction of c-MYC and cyclin D1 genes, and blocks CSF-1-dependent progression through the G1 phase of the cell cycle. We devis...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Davis JN,Rock CO,Cheng M,Watson JB,Ashmun RA,Kirk H,Kay RJ,Roussel MF

    更新日期:1997-12-01 00:00:00

  • Mechanism of R-loop formation at immunoglobulin class switch sequences.

    abstract::R-loops have been described in vivo at the immunoglobulin class switch sequences and at prokaryotic and mitochondrial origins of replication. However, the biochemical mechanism and determinants of R-loop formation are unclear. We find that R-loop formation is nearly eliminated when RNase T(1) is added during transcrip...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Roy D,Yu K,Lieber MR

    更新日期:2008-01-01 00:00:00

  • Complex recognition site for the group I intron-encoded endonuclease I-SceII.

    abstract::We have characterized features of the site recognized by a double-stranded DNA endonuclease, I-SceII, encoded by intron 4 alpha of the yeast mitochondrial COX1 gene. We determined the effects of 36 point mutations on the cleavage efficiency of natural and synthetic substrates containing the Saccharomyces capensis I-Sc...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Wernette C,Saldanha R,Smith D,Ming D,Perlman PS,Butow RA

    更新日期:1992-02-01 00:00:00

  • Poly(A) signals located near the 5' end of genes are silenced by a general mechanism that prevents premature 3'-end processing.

    abstract::Poly(A) signals located at the 3' end of eukaryotic genes drive cleavage and polyadenylation at the same end of pre-mRNA. Although these sequences are expected only at the 3' end of genes, we found that strong poly(A) signals are also predicted within the 5' untranslated regions (UTRs) of many Drosophila melanogaster ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Guo J,Garrett M,Micklem G,Brogna S

    更新日期:2011-02-01 00:00:00

  • Genetic mapping of Ty elements in Saccharomyces cerevisiae.

    abstract::We used transformation to insert a selectable marker at various sites in the Saccharomyces cerevisiae genome occupied by the transposable element Ty. The vector CV9 contains the LEU2+ gene and a portion of the repeated element Ty1-17. Transformation with this plasmid resulted in integration of the vector via a recipro...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Klein HL,Petes TD

    更新日期:1984-02-01 00:00:00

  • Inhibition of chicken embryo lens differentiation and lens junction formation in culture by pp60v-src.

    abstract::A culture system was developed which permitted the differentiation of chicken lens epithelial cells to lentoid bodies which contained several cell layers, accumulated high levels of delta-crystallin, and produced extensive gap junctions. This differentiation process was prevented when the cells were infected with a te...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Menko AS,Boettiger D

    更新日期:1988-04-01 00:00:00

  • Isolation and characterization of a novel epithelium-specific transcription factor, ESE-1, a member of the ets family.

    abstract::We report here the isolation of a novel, highly tissue-restricted member of the ets transcription factor/oncogene family, ESE-1 (for epithelium-specific Ets), which has features distinct from those of any other ets-related factor. ESE-1 contains two putative DNA binding domains: an ETS domain, which is unique in that ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Oettgen P,Alani RM,Barcinski MA,Brown L,Akbarali Y,Boltax J,Kunsch C,Munger K,Libermann TA

    更新日期:1997-08-01 00:00:00

  • Ligand-induced repression of the glucocorticoid receptor gene is mediated by an NCoR1 repression complex formed by long-range chromatin interactions with intragenic glucocorticoid response elements.

    abstract::Glucocorticoids are among the most potent and effective agents for treating inflammatory diseases and hematological cancers. However, subpopulations of patients are often resistant to steroid therapy, and determining the molecular mechanisms that contribute to glucocorticoid resistance is thus critical to addressing t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Ramamoorthy S,Cidlowski JA

    更新日期:2013-05-01 00:00:00

  • Transforming Growth Factor β-Induced Proliferative Arrest Mediated by TRIM26-Dependent TAF7 Degradation and Its Antagonism by MYC.

    abstract::Recognition of gene promoters by RNA polymerase II is mediated by general transcription factor IID (TFIID), which has been thought to be a static complex and to play a passive role in the regulation of gene expression under the instruction of gene-specific transcription factors. Here we show that transforming growth f...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Nakagawa T,Hosogane M,Nakagawa M,Morohoshi A,Funayama R,Nakayama K

    更新日期:2018-02-12 00:00:00