Abstract:
:Unique among fibroblast growth factors (FGFs), FGF19, -21, and -23 act in an endocrine fashion to regulate energy, bile acid, glucose, lipid, phosphate, and vitamin D homeostasis. These FGFs require the presence of Klotho/betaKlotho in their target tissues. Here, we present the crystal structures of FGF19 alone and FGF23 in complex with sucrose octasulfate, a disaccharide chemically related to heparin. The conformation of the heparin-binding region between beta strands 10 and 12 in FGF19 and FGF23 diverges completely from the common conformation adopted by paracrine-acting FGFs. A cleft between this region and the beta1-beta2 loop, the other heparin-binding region, precludes direct interaction between heparin/heparan sulfate and backbone atoms of FGF19/23. This reduces the heparin-binding affinity of these ligands and confers endocrine function. Klotho/betaKlotho have evolved as a compensatory mechanism for the poor ability of heparin/heparan sulfate to promote binding of FGF19, -21, and -23 to their cognate receptors.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Goetz R,Beenken A,Ibrahimi OA,Kalinina J,Olsen SK,Eliseenkova AV,Xu C,Neubert TA,Zhang F,Linhardt RJ,Yu X,White KE,Inagaki T,Kliewer SA,Yamamoto M,Kurosu H,Ogawa Y,Kuro-o M,Lanske B,Razzaque MS,Mohammadi Mdoi
10.1128/MCB.02249-06subject
Has Abstractpub_date
2007-05-01 00:00:00pages
3417-28issue
9eissn
0270-7306issn
1098-5549pii
MCB.02249-06journal_volume
27pub_type
杂志文章abstract::The essential Saccharomyces cerevisiae gene BDP1 encodes a subunit of RNA polymerase III (Pol III) transcription factor (TFIIIB); TATA box binding protein (TBP) and Brf1 are the other subunits of this three-protein complex. Deletion analysis defined three segments of Bdp1 that are essential for viability. A central se...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.10.3264-3275.2002
更新日期:2002-05-01 00:00:00
abstract::Tetraspanins are clustered in specific microdomains (named tetraspanin-enriched microdomains, or TERM) in the plasma membrane and regulate the functions of associated transmembrane receptors, including integrins and receptor tyrosine kinases. We have identified syntenin-1, a PDZ domain-containing protein, as a new com...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00849-06
更新日期:2006-10-01 00:00:00
abstract::The ribosomal proteins (RPs) of Saccharomyces cerevisiae are encoded by 137 genes that are among the most transcriptionally active in the genome. These genes are coordinately regulated: a shift up in temperature leads to a rapid, but temporary, decline in RP mRNA levels. A defect in any part of the secretory pathway l...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.8.5393
更新日期:1999-08-01 00:00:00
abstract::The phorbol ester receptor protein kinase C (PKC) gene family encodes essential mediators of eukaryotic cellular signals. Molecular dissection of their mechanisms of action has been limited in part by the lack of random mutagenesis approaches and by the complexity of signaling pathways in mammalian cells which involve...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.8.4728
更新日期:1993-08-01 00:00:00
abstract::Liu and Mertz (Genes Dev. 9:1766-1780, 1995) previously identified a 119-nt pre-mRNA processing enhancer (PPE) element within the herpes simplex virus type 1 thymidine kinase gene that enables intron-independent gene expression in higher eukaryotes by binding heterogeneous nuclear ribonucleoprotein L (hnRNP L). Here, ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.15.6303-6313.2005
更新日期:2005-08-01 00:00:00
abstract::Cse4p is a variant of histone H3 that has an essential role in chromosome segregation and centromere chromatin structure in budding yeast. Cse4p has a unique 135-amino-acid N terminus and a C-terminal histone-fold domain that is more than 60% identical to histone H3 and the mammalian centromere protein CENP-A. Cse4p a...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.9.6130
更新日期:1999-09-01 00:00:00
abstract::The conserved RNA binding protein La recognizes UUU-3'OH on its small nuclear RNA ligands and stabilizes them against 3'-end-mediated decay. We report that newly described La-related protein 4 (LARP4) is a factor that can bind poly(A) RNA and interact with poly(A) binding protein (PABP). Yeast two-hybrid analysis and ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01162-10
更新日期:2011-02-01 00:00:00
abstract::TRAIL is an endogenous death receptor ligand also used therapeutically because of its selective proapoptotic activity in cancer cells. In the present study, we examined chromatin alterations induced by TRAIL and show that TRAIL induces a rapid activation of DNA damage response (DDR) pathways with histone H2AX, Chk2, A...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00581-08
更新日期:2009-01-01 00:00:00
abstract::Ribosomal (r) proteins encoded by polyadenylated RNA were specifically precipitated in vitro from polysomes by using antibodies raised against characterized Drosophila melanogaster r proteins. The immuno-purified mRNA in the polysome complex was used to prepare cDNA with which to probe a D. melanogaster genomic librar...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.12.2643
更新日期:1984-12-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.2.808-818.2005
更新日期:2005-01-01 00:00:00
abstract::We have cloned and sequenced the CRY1 gene, encoding ribosomal protein S14 in Chlamydomonas reinhardtii, and found that it is highly similar to S14/rp59 proteins from other organisms, including mammals, Drosophila melanogaster, and Saccharomyces cerevisiae. We isolated a mutant strain resistant to the eukaryotic trans...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.6.4011
更新日期:1994-06-01 00:00:00
abstract::DNA mismatch repair maintains genomic stability by detecting and correcting mispaired DNA sequences and by signaling cell death when DNA repair fails. The mechanism by which mismatch repair coordinates DNA damage and repair with cell survival or death is not understood, but it suggests the need for regulation. Since t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.9.3320-3328.2003
更新日期:2003-05-01 00:00:00
abstract::The heat shock transcription factors (Hsfs) activate the stress-inducible expression of heat shock proteins (Hsps) and other molecular chaperones in response to stress and, therefore, play an essential role in protein disaggregation and protein folding. In humans, missense mutation in the hsf4 gene causes cataract, an...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.8.3282-3294.2006
更新日期:2006-04-01 00:00:00
abstract::Precursor RNA containing the adenovirus L3 polyadenylation site is assembled into a 50S complex upon incubation with HeLa nuclear extract at 30 degrees C. The cofactor and sequence requirements for 50S complex formation are similar to those of the in vitro polyadenylation reaction. Assembly of this complex requires AT...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.1.226
更新日期:1988-01-01 00:00:00
abstract::Growth differentiation factor 15 (GDF15) is a secreted protein with pleotropic functions from the transforming growth factor β (TGF-β) family. GDF15 is synthesized as a precursor and undergoes proteolytic cleavage to generate mature GDF15. The strong appetite-suppressing effect of mature GDF15 makes it an attractive t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00249-18
更新日期:2018-10-15 00:00:00
abstract::Heterogeneous nuclear RNA contains double-stranded regions that are not found in mRNA and that may serve as recognition elements for processing enzymes. The double-stranded regions of heterogeneous nuclear RNA prepared from HeLa cells promoted the synthesis of (2',5')oligoadenylate [(2',5')oligo(A) or (2'5')An] when i...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.2.2.154
更新日期:1982-02-01 00:00:00
abstract::A molecular karyotype of Neurospora crassa was obtained by using an alternating-field gel electrophoresis system which employs contour-clamped homogeneous electric fields. The migration of all seven N. crassa chromosomal DNAs was defined, and five of the seven molecules were separated from one another. The estimated s...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.4.1469
更新日期:1988-04-01 00:00:00
abstract::The intracellular accumulation of the unspliced RNA of Rous sarcoma virus was decreased when translation was prematurely terminated by the introduction of nonsense codons within its 5' proximal gene, the gag gene. Subcellular fractionation of transfected cells suggested that nonsense codon-mediated instability occurre...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.3.1986
更新日期:1994-03-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.10.5634
更新日期:1998-10-01 00:00:00
abstract::Most mammalian genes produce transcripts whose 3' ends are processed at multiple alternative positions by cleavage/polyadenylation (CPA). Poly(A) site cleavage frequently occurs cotranscriptionally and is facilitated by CPA factor binding to the RNA polymerase II (Pol II) C-terminal domain (CTD) phosphorylated on Ser2...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00898-15
更新日期:2015-11-02 00:00:00
abstract::During the functional analysis of open reading frames (ORFs) identified during the sequencing of chromosome III of Saccharomyces cerevisiae, the previously uncharacterized ORF YCL031C (now designated RRP7) was deleted. RRP7 is essential for cell viability, and a conditional null allele was therefore constructed, by pl...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.9.5023
更新日期:1997-09-01 00:00:00
abstract::Following chromosome duplication in S phase of the cell cycle, the sister chromatids are linked by cohesin. At the onset of anaphase, separase cleaves cohesin and thereby initiates sister chromatid separation. Separase activation results from the destruction of its inhibitor, securin, which is triggered by a ubiquitin...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00235-08
更新日期:2008-09-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00290-10
更新日期:2010-07-01 00:00:00
abstract::An ACG codon, which replaces the AUG codon used to initiate the synthesis of bacteriophage T7 gene 0.3 protein, was shown to function as a low-efficiency initiation codon in a wheat germ cell-free protein-synthesizing system. ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.5.12.3621
更新日期:1985-12-01 00:00:00
abstract::Despite distinct dissimilarities, diverse cancers express several common protumorigenic traits. We present here evidence that the proapoptotic protein Par-4 utilizes one such common tumorigenic trait to become selectively activated and induce apoptosis in cancer cells. Elevated protein kinase A (PKA) activity noted in...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.3.1146-1161.2005
更新日期:2005-02-01 00:00:00
abstract::We have initiated a study of the promoter region of the alkaline extracellular protease gene (XPR2) from Yarrowia lipolytica to identify upstream sequences possibly involved in carbon, nitrogen, and peptone control of XPR2 expression. Deletion analysis showed that the TATA box and two major upstream activation sequenc...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.1.327
更新日期:1994-01-01 00:00:00
abstract::The protein tyrosine kinase c-Src is regulated by two intramolecular interactions. The repressed state is achieved through the interaction of the Src homology 2 (SH2) domain with the phosphorylated C-terminal tail and the association of the SH3 domain with a polyproline type II helix formed by the linker region betwee...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.02014-06
更新日期:2007-03-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.10.5579
更新日期:1996-10-01 00:00:00
abstract::Translation is a fundamental step in gene expression, and translational control is exerted in many developmental processes. Most eukaryotic mRNAs are translated by a cap-dependent mechanism, which requires recognition of the 5'-cap structure of the mRNA by eukaryotic translation initiation factor 4E (eIF4E). eIF4E act...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01354-12
更新日期:2013-08-01 00:00:00
abstract::The interaction of enhancers with different promoters was studied by measuring the influence of two enhancers (from simian virus 40 and from Harvey sarcoma virus) on the activity of expression vectors that are identical except for their promoter region. The promoters examined were from the simian virus 40 early region...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.4.8.1664
更新日期:1984-08-01 00:00:00