Abstract:
:The dynamic SCF (Skp1-cullin1-F-box protein) assembly is controlled by cycles of cullin neddylation/deneddylation based on the deneddylation activity of the COP9 signalosome (CSN) and global sequestration of cullins by CAND1. However, acceptance of this prediction was hampered by the results of recent studies, and the regulatory mechanism and key players remain to be identified. We found that maintaining a proper Cul1Nedd8/Cul1 ratio is crucial to ensure SCF functions. Reducing the high Cul1Nedd8/Cul1 ratios in csn mutants through ectopic expression of the nonneddylatable Cul1K722R proteins or introducing the endogenous cul1 K722R point mutation significantly rescues their defective phenotypes. In vivo protein degradation assays revealed that the large portion of the unneddylated Cul1 contributes to F-box protein stabilization. Moreover, the unneddylated Cul1 tends to associate with adaptor modules, and disruption of Cul1-Skp-1 binding fails to restore the csn phenotypes. Taking the data together, we propose that unneddylated Cul1 is another central player involved in maintenance of the adaptor module pool through the formation of Cul1-Skp-1-F-box complexes and promotion of rapid SCF assembly.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Liu Q,Zhou Y,Tang R,Wang X,Hu Q,Wang Y,He Qdoi
10.1128/MCB.00109-17subject
Has Abstractpub_date
2017-11-13 00:00:00issue
23eissn
0270-7306issn
1098-5549pii
MCB.00109-17journal_volume
37pub_type
杂志文章abstract::Nutrients, drugs, and hormones influence transcription during differentiation and metabolism by binding to high-affinity nuclear receptors. In the absence of ligand, some but not all nuclear receptors repress transcription as a heterodimer with retinoid X receptor (RXR). Here we define a novel role for helix 12 (H12) ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.9.6448
更新日期:1999-09-01 00:00:00
abstract::The Ras pathway transduces divergent signals determining normal cell fate and is frequently activated in hematopoietic malignancies, but the manner in which activation contributes to human leukemia is poorly understood. We report that a high level of activated H-Ras signaling in transduced primary human hematopoietic ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.16.6993-7002.2004
更新日期:2004-08-01 00:00:00
abstract::Nuclear receptors (NRs) regulate diverse physiological processes, including the central nervous system control of energy balance. However, the molecular mechanisms for the central actions of NRs in energy balance remain relatively poorly defined. Here we report a hypothalamic gene network involving two NRs, neuron-der...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00385-13
更新日期:2013-10-01 00:00:00
abstract::Imprinted genes are expressed in a monoallelic, parent-of-origin-specific manner. Clusters of imprinted genes are regulated by imprinting control regions (ICRs) characterized by DNA methylation of one allele. This methylation is critical for imprinting; a reduction in the DNA methyltransferase DNMT1 causes a widesprea...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01278-09
更新日期:2010-08-01 00:00:00
abstract::The NuA4 histone acetyltransferase (HAT) multisubunit complex is responsible for acetylation of histone H4 and H2A N-terminal tails in yeast. Its catalytic component, Esa1, is essential for cell cycle progression, gene-specific regulation and has been implicated in DNA repair. Almost all NuA4 subunits have clear homol...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.24.5.1884-1896.2004
更新日期:2004-03-01 00:00:00
abstract::Receptor tyrosine kinases (RTKs) play distinct roles in multiple biological systems. Many RTKs transmit similar signals, raising questions about how specificity is achieved. One potential mechanism for RTK specificity is control of the magnitude and kinetics of activation of downstream pathways. We have found that the...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.22.12.4062-4072.2002
更新日期:2002-06-01 00:00:00
abstract::Miz1 is a member of the POZ domain/zinc finger transcription factor family. In vivo, Miz1 forms a complex with the Myc oncoprotein and recruits Myc to core promoter elements. Myc represses transcription through Miz1 binding sites. We now show that the Miz1 gene is ubiquitously expressed during mouse embryogenesis. In ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.21.7648-7657.2003
更新日期:2003-11-01 00:00:00
abstract::Oncostatin M is a polypeptide cytokine, produced by normal and malignant hematopoietic cells, that has several in vitro activities, including the ability to inhibit growth of cultured carcinoma cells. Here we present a structural and functional comparison of two oncostatin M-related proteins (Mr 36,000 and 32,000) sec...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.5.1882
更新日期:1990-05-01 00:00:00
abstract::Intron-encoded U17a and U17b RNAs are members of the H/ACA-box class of small nucleolar RNAs (snoRNAs) participating in rRNA processing and modification. We have investigated the organization and expression of the U17 locus in human cells and found that intronic U17a and U17b sequences are transcribed as part of the t...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.8.4509
更新日期:1998-08-01 00:00:00
abstract::zfh-1 is a member of the zfh family of proteins, which all contain zinc finger and homeodomains. The roles and mechanisms of action of most family members are still unclear. However, we have shown previously that another member of the family, the vertebrate ZEB protein, is a transcriptional repressor that binds E box ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.10.7255
更新日期:1999-10-01 00:00:00
abstract::The removal of oxidative damage from Saccharomyces cerevisiae DNA is thought to be conducted primarily through the base excision repair pathway. The Escherichia coli endonuclease III homologs Ntg1p and Ntg2p are S. cerevisiae N-glycosylase-associated apurinic/apyrimidinic (AP) lyases that recognize a wide variety of d...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.4.2929
更新日期:1999-04-01 00:00:00
abstract::The transcriptional regulating protein of 132 kDa (TReP-132) has been identified in steroidogenic tissues, where it acts as a coactivator of steroidogenic factor 1 (SF-1). We show here that TReP-132 plays a role in the control of cell proliferation. In human HeLa cells, TReP-132 knockdown by using small interfering RN...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.11.4335-4348.2005
更新日期:2005-06-01 00:00:00
abstract::Much of the regulatory diversity in eukaryotic transcription is provided by coregulators, which are recruited by DNA-binding factors to propagate signaling to basal machinery or chromatin. p160 family members, including the glucocorticoid receptor (GR)-interacting protein 1 (GRIP1), function as coactivators for GR, a ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.06473-11
更新日期:2012-02-01 00:00:00
abstract::Exposure of phosphatidylserine (PS) on the cell surface occurs early during apoptosis and serves as a recognition signal for phagocytes. Clearance of apoptotic cells by a membrane PS receptor is one of the critical anti-inflammatory functions of macrophages. However, the PS binding receptors and their recognition mech...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01993-07
更新日期:2008-09-01 00:00:00
abstract::Activating mutations in KEAP1-NRF2 are frequently found in tumors of the lung, esophagus, and liver, where they are associated with aggressive growth, resistance to cancer therapies, and low overall survival. Despite the fact that NRF2 is a validated driver of tumorigenesis and chemotherapeutic resistance, there are c...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00377-20
更新日期:2020-10-26 00:00:00
abstract::Signal transducers and activators of transcription (STATs) are transcription factors that mediate normal biologic responses to cytokines and growth factors. However, abnormal activation of certain STAT family members, including Stat3, is increasingly associated with oncogenesis. In fibroblasts expressing the Src oncop...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.11.7519
更新日期:1999-11-01 00:00:00
abstract::Max is a basic helix-loop-helix/leucine zipper protein that forms heterodimers with the Myc family of proteins to promote cell growth and with the Mad/Mxi1 family of proteins to inhibit cell growth. The role of Max as the obligate binding partner for these two protein families necessitates the observed constitutive ex...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.3.1037
更新日期:1997-03-01 00:00:00
abstract::The DNA and protein complex known as chromatin is subject to posttranslational modifications (PTMs) that regulate cellular functions such that PTM dysregulation can lead to disease, including cancer. One critical PTM is acetylation/deacetylation, which is being investigated as a means to develop targeted cancer therap...
journal_title:Molecular and cellular biology
pub_type: 杂志文章,评审
doi:10.1128/MCB.00232-20
更新日期:2020-08-28 00:00:00
abstract::The Saccharomyces cerevisiae PGK (phosphoglycerate kinase) gene encodes one of the most abundant mRNA and protein species in the cell. To identify the promoter sequences required for the efficient expression of PGK, we undertook a detailed internal deletion analysis of the 5' noncoding region of the gene. Our analysis...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.12.4335
更新日期:1986-12-01 00:00:00
abstract::Prdm1/Blimp-1 is a master regulator of gene expression in diverse tissues of the developing embryo and adult organism. Its C-terminal zinc finger domain mediates nuclear import, DNA binding, and recruitment of the corepressors G9a and HDAC1/2. Alternatively spliced transcripts lacking exon 7 sequences encode a structu...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00174-12
更新日期:2012-09-01 00:00:00
abstract::We previously established that the phage phiC31 integrase, a site-specific recombinase, mediates efficient integration in the human cell environment at attB and attP phage attachment sites on extrachromosomal vectors. We show here that phage attP sites inserted at various locations in human and mouse chromosomes serve...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.12.3926-3934.2001
更新日期:2001-06-01 00:00:00
abstract::Menin, the product of the multiple endocrine neoplasia type I gene, has been implicated in several biological processes, including the control of gene expression and apoptosis, the modulation of mitogen-activated protein kinase pathways, and DNA damage sensing or repair. In this study, we have investigated the functio...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.22.9960-9972.2005
更新日期:2005-11-01 00:00:00
abstract::The neutral/neutral two-dimensional (2-D) gel replicon mapping technique has been used to great advantage to localize and characterize origins of replication. Interestingly, many yeast origins display a composite pattern consisting of both a bubble arc and a single-fork arc. Moreover, in every instance in which neutra...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.9.4915
更新日期:1996-09-01 00:00:00
abstract::Here, we demonstrate that elevation of intracellular cyclic AMP (cAMP) in vascular endothelial cells (ECs) by either a direct activator of adenylyl cyclase or endogenous cAMP-mobilizing G protein-coupled receptors inhibited the tyrosine phosphorylation of STAT proteins by an interleukin 6 (IL-6) receptor trans-signali...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00207-06
更新日期:2006-09-01 00:00:00
abstract::The baker's yeast Saccharomyces cerevisiae possesses a single gene encoding heat shock transcription factor (HSF), which is required for the activation of genes that participate in stress protection as well as normal growth and viability. Yeast HSF (yHSF) contains two distinct transcriptional activation regions locate...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.11.6340
更新日期:1998-11-01 00:00:00
abstract::Ubiquitin is a multifunctional 76-amino-acid protein which plays critical roles in many aspects of cellular metabolism. In Caenorhabditis elegans, the major source of ubiquitin RNA is the polyubiquitin locus, UbiA. UbiA is transcribed as a polycistronic mRNA which contains 11 tandem repeats of ubiquitin sequence and p...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.1.268
更新日期:1989-01-01 00:00:00
abstract::In Saccharomyces cerevisiae, the protein phosphatase type 1 (PP1)-binding protein Reg1 is required to maintain complete repression of ADH2 expression during growth on glucose. Surprisingly, however, mutant forms of the yeast PP1 homologue Glc7, which are unable to repress expression of another glucose-regulated gene, ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.9.6029
更新日期:1999-09-01 00:00:00
abstract::Protein tyrosine kinase Pyk2 is activated by a variety of G-protein-coupled receptors and by extracellular signals that elevate intracellular Ca2+ concentration. We have identified a new Pyk2 binding protein designated Pap. Pap is a multidomain protein composed of an N-terminal alpha-helical region with a coiled-coil ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.3.2338
更新日期:1999-03-01 00:00:00
abstract::Mammalian GRP78/BiP is a stress-inducible 78-kDa endoplasmic reticulum (ER) protein with molecular chaperone and calcium-binding properties. The transactivation of grp78 by the calcium ionophore A23187 provides a model system with which to study the signal transduction that allows mammalian cells to sense calcium depl...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.4.2263
更新日期:1995-04-01 00:00:00
abstract::The interleukin-2 receptor (IL-2R) beta chain (IL-2R beta) is an essential signaling component of high- and intermediate-affinity IL-2Rs. Our laboratory previously reported that a DNA fragment containing 857 bp of 5'-flanking sequence of the human IL-2R beta gene exhibited promoter activity. We have now further charac...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.10.6201
更新日期:1993-10-01 00:00:00