Abstract:
:Activation of canonical Wnt signaling inhibits brown adipogenesis of cultured cells by impeding induction of PPARgamma and C/EBPalpha. Although enforced expression of these adipogenic transcription factors restores lipid accumulation and expression of FABP4 in Wnt-expressing cells, additional expression of PGC-1alpha is required for activation of uncoupling protein 1 (UCP1). Wnt10b blocks brown adipose tissue development and expression of UCP1 when expressed from the fatty acid binding protein 4 promoter, even when mice are administered a beta3-agonist. In differentiated brown adipocytes, activation of Wnt signaling suppresses expression of UCP1 through repression of PGC-1alpha. Consistent with these in vitro observations, UCP1-Wnt10b transgenic mice, which express Wnt10b in interscapular tissue, lack functional brown adipose tissue. While interscapular tissue of UCP1-Wnt10b mice lacks expression of PGC-1alpha and UCP1, the presence of unilocular lipid droplets and expression of white adipocyte genes suggest conversion of brown adipose tissue to white. Reciprocal expression of Wnt10b with UCP1 and PGC-1alpha in interscapular tissue from cold-challenged or genetically obese mice provides further evidence for regulation of brown adipocyte metabolism by Wnt signaling. Taken together, these data suggest that activation of canonical Wnt signaling early in differentiation blocks brown adipogenesis, whereas activating Wnt signaling in mature brown adipocytes stimulates their conversion to white adipocytes.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Kang S,Bajnok L,Longo KA,Petersen RK,Hansen JB,Kristiansen K,MacDougald OAdoi
10.1128/MCB.25.4.1272-1282.2005subject
Has Abstractpub_date
2005-02-01 00:00:00pages
1272-82issue
4eissn
0270-7306issn
1098-5549pii
25/4/1272journal_volume
25pub_type
杂志文章abstract::Previous analyses defined a proliferating cell nuclear antigen (PCNA) E1A-responsive element (PERE) in the PCNA promoter that is essential for transactivation by the 243-residue product of the adenovirus type 2 E1A 12S mRNA (E1A 243R). In this report, we show that the PERE activates a heterologous basal promoter and c...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.1.543
更新日期:1994-01-01 00:00:00
abstract::The Moloney murine sarcoma virus long terminal repeat (LTR) harbors two distinct positive activators of transcription, namely, a distal signal and an enhancer. In this report we demonstrate that infection by herpes simplex virus (HSV) can markedly affect the utilization of these two Moloney murine sarcoma virus transc...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.8.1959
更新日期:1985-08-01 00:00:00
abstract::There are five members of the RFX family of transcription factors in mammals. While RFX5 plays a well-defined role in the immune system, the functions of RFX1 to RFX4 remain largely unknown. We have generated mice with a deletion of the Rfx3 gene. RFX3-deficient mice exhibit frequent left-right (LR) asymmetry defects ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.24.10.4417-4427.2004
更新日期:2004-05-01 00:00:00
abstract::In the accompanying report (C. F. Webb, C. Das, S. Eaton, K. Calame, and P. Tucker, Mol. Cell. Biol. 11:5197-5205, 1991), we characterize B-cell-specific protein-DNA interactions at -500 and -200 bp upstream of the mu immunoglobulin heavy chain promoter whose abundances were increased by interleukin-5 plus antigen. Be...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.10.5206
更新日期:1991-10-01 00:00:00
abstract::Simultaneous resistance to an array of drugs with different cytotoxic activities is a property of Saccharomyces cerevisiae, in which the protein Pdr3p has recently been shown to play a role as a transcriptional regulator. We provide evidence that the yeast PDR3 gene, which encodes a zinc finger transcription factor im...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.8.4043
更新日期:1995-08-01 00:00:00
abstract::The human immunodeficiency virus type 1 (HIV-1) Tat protein activates transcription elongation by stimulating the Tat-activated kinase (TAK/p-TEFb), a protein kinase composed of CDK9 and its cyclin partner, cyclin T1. CDK9 is able to hyperphosphorylate the carboxyl-terminal domain (CTD) of the large subunit of RNA pol...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.4.1079-1093.2002
更新日期:2002-02-01 00:00:00
abstract::c-Myc promotes apoptosis by destabilizing mitochondrial integrity, leading to the release of proapoptotic effectors including holocytochrome c. Candidate mediators of c-Myc in this process are the proapoptotic members of the Bcl-2 family. We show here that fibroblasts lacking Bak remain susceptible to c-Myc-induced ap...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.17.6158-6169.2002
更新日期:2002-09-01 00:00:00
abstract::CAP, a protein from Saccharomyces cerevisiae that copurifies with adenylyl cyclase, appears to be required for yeast cells to be fully responsive to RAS proteins. CAP also appears to be required for normal cell morphology and responsiveness to nutrient deprivation and excess. We describe here a molecular and phenotypi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.3.1248
更新日期:1991-03-01 00:00:00
abstract::The action of insulin to recruit the intracellular GLUT4 glucose transporter to the plasma membrane of 3T3-L1 adipocytes is mimicked by endothelin 1, which signals through trimeric G(alpha)q or G(alpha)11 proteins. Here we report that murine G(alpha)11 is most abundant in fat and that expression of the constitutively ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.15.5262-5275.2001
更新日期:2001-08-01 00:00:00
abstract::Topoisomerase I cleavage complexes can be induced by a variety of DNA damages and by the anticancer drug camptothecin. We have developed a ligation-mediated PCR (LM-PCR) assay to analyze replication-mediated DNA double-strand breaks induced by topoisomerase I cleavage complexes in human colon carcinoma HT29 cells at t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.11.3977-3987.2000
更新日期:2000-06-01 00:00:00
abstract::Rats and mice have two, equally expressed, nonallelic genes encoding preproinsulin (genes I and II). Cytological hybridization with metaphase chromosomes indicated that both genes reside on rat chromosome I but are approximately 100,000 kilobases apart. In mice the two genes reside on two different chromosomes. DNA se...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.8.2090
更新日期:1985-08-01 00:00:00
abstract::Sortilin is a member of the Vps10p domain family of neuropeptide and neurotrophin binding neuronal receptors. The family members interact with and partly share a variety of ligands and partake in intracellular sorting and protein transport as well as in transmembrane signal transduction. Thus, sortilin mediates the tr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00274-10
更新日期:2010-09-01 00:00:00
abstract::The DNA-binding transcriptional activator Gal4 and its regulators Gal80 and Gal3 constitute a galactose-responsive switch for the GAL genes of Saccharomyces cerevisiae. Gal4 binds to GAL gene UASGAL (upstream activation sequence in GAL gene promoter) sites as a dimer via its N-terminal domain and activates transcripti...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00646-12
更新日期:2013-09-01 00:00:00
abstract::Cell adhesion and spreading depend on activation of mitogen-activated kinase, which in turn is regulated both by growth factor and integrin signaling. Growth factors, such as epidermal growth factor, are capable of activating Ras and Raf, but integrin signaling is required to couple Raf to MEK and MEK to extracellular...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.24.6.2308-2317.2004
更新日期:2004-03-01 00:00:00
abstract::Transposons have contributed protein coding sequences to a unexpectedly large number of human genes. Except for the V(D)J recombinase and telomerase, all remain of unknown function. Here we investigate the activity of the human SETMAR protein, a highly expressed fusion between a histone H3 methylase and a mariner fami...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01899-06
更新日期:2007-02-01 00:00:00
abstract::The upstream promoter sequences of the human carbonic anhydrase II (CA II) gene have been studied by 5' deletion analysis. Promoter activity was assayed by transfection and chloramphenicol acetyltransferase assay in both human HeLa cells and murine L cells. This investigation showed that the CA II promoter is comparab...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.12.4589
更新日期:1987-12-01 00:00:00
abstract::Inactivation of the tumor suppressor p53 by degradation is a mechanism utilized by cells to adapt to endoplasmic reticulum (ER) stress. However, the mechanisms of p53 destabilization by ER stress are not known. We demonstrate here that the E3 ubiquitin-ligase Hdm2 is essential for the nucleocytoplasmic transport and p...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.21.9392-9405.2005
更新日期:2005-11-01 00:00:00
abstract::Autophagy is considered an adaptive mechanism against hyperosmotic stress. Although the process has been reported to be triggered by the inhibition of mTORC1, the precise downstream mechanisms remain elusive. Here, we demonstrate that hyperosmotic-stress-induced autophagy is different from conventional macroautophagy ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00024-19
更新日期:2019-07-29 00:00:00
abstract::Muscle wasting (cachexia) is a consequence of chronic diseases, such as cancer, and is associated with degradation of muscle proteins such as MyoD. The cytokines tumor necrosis factor alpha and gamma interferon induce muscle degeneration by activating the transcription factor NF-kappaB and its target genes. Here, we s...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.15.6533-6545.2005
更新日期:2005-08-01 00:00:00
abstract::Enhancer elements modulate promoter activity over vast chromosomal distances, and mechanisms that ensure restrictive interactions between promoters and enhancers are critical for proper control of gene expression. The human beta-globin locus control region (LCR) activates expression of five genes in erythroid cells, i...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00602-07
更新日期:2007-08-01 00:00:00
abstract::It is well established that cell survival signals stimulated by growth factors, cytokines, and oncoproteins are initiated by phosphoinositide 3-kinase (PI3K)- and Akt-dependent signal transduction pathways. Oncogenic Ras, an upstream activator of Akt, requires NF-kappaB to initiate transformation, at least partially t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.5.1626-1638.2000
更新日期:2000-03-01 00:00:00
abstract::We utilized the human 4F2 heavy-chain (4F2HC) gene as a model system to study the regulation of inducible gene expression during normal human T-cell activation. Previous studies have demonstrated that 4F2HC gene expression is induced during normal T-cell activation and that the activity of the gene is regulated, at le...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.6.2588
更新日期:1989-06-01 00:00:00
abstract::Posttranslational modification of general transcription factors may be an important mechanism for global gene regulation. The general transcription factor IIA (TFIIA) binds to the TATA binding protein (TBP) and is essential for high-level transcription mediated by various activators. Modulation of the TFIIA-TBP intera...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.4.2846
更新日期:1999-04-01 00:00:00
abstract::In this report, we document an unusual mode of tissue-enriched gene expression that is primarily mediated by alternative and inefficient splicing. We have analyzed posttranscriptional regulation of the Drosophila erect wing gene, which provides a vital neuronal function and is essential for the formation of certain mu...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.6.3998
更新日期:1999-06-01 00:00:00
abstract::Although TRAIL is considered a potential anticancer agent, it enhances tumor progression by activating NF-κB in apoptosis-resistant cells. Cellular FLICE-like inhibitory protein (cFLIP) overexpression and caspase-8 activation have been implicated in TRAIL-induced NF-κB activation; however, the underlying mechanisms ar...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00692-15
更新日期:2015-10-01 00:00:00
abstract::Kinase-negative mutants of S49 mouse lymphoma cells, which lack detectable catalytic (C) subunit of cyclic AMP-dependent protein kinase, nevertheless contain cytoplasmic mRNAs for the two major forms of C subunit, C alpha and C beta. Investigation of the metabolism of C subunits in wild-type and mutant cells was under...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.2.705
更新日期:1991-02-01 00:00:00
abstract::RNA editing in trypanosomes has been proposed to occur through transesterification or endonuclease cleavage and RNA ligation reactions. Both models involve a chimeric intermediate in which a guide RNA (gRNA) is joined through its 3' oligo(U) tail to an editing site of the corresponding mRNA. Velocity centrifugation of...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.6.2925
更新日期:1995-06-01 00:00:00
abstract::Unlike Saccharomyces cerevisiae RNA polymerase III, human RNA polymerase III has not been entirely characterized. Orthologues of the yeast RNA polymerase III subunits C128 and C37 remain unidentified, and for many of the other subunits, the available information is limited to database sequences with various degrees of...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.22.8044-8055.2002
更新日期:2002-11-01 00:00:00
abstract::Polycomb repressive complexes (PRCs) are important chromatin regulators of embryonic stem (ES) cell function. RYBP binds Polycomb H2A monoubiquitin ligases Ring1A and Ring1B and has been suggested to assist PRC localization to their targets. Moreover, constitutive inactivation of RYBP precludes ES cell formation. Usin...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.06441-11
更新日期:2012-03-01 00:00:00
abstract::Thrombospondins are a family of stress-inducible secreted glycoproteins that underlie tissue remodeling. We recently reported that thrombospondin-4 (Thbs4) has a critical intracellular function, regulating the adaptive endoplasmic reticulum (ER) stress pathway through activating transcription factor 6α (Atf6α). In the...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00607-15
更新日期:2015-10-12 00:00:00