Abstract:
:The ubiquitin-specific protease (USP) family is the largest group of cysteine proteases. Cancer genomic analysis identified frequent amplification of USP21 (22%) in human pancreatic ductal adenocarcinoma (PDAC). USP21 overexpression correlates with human PDAC progression, and enforced expression of USP21 accelerates murine PDAC tumor growth and drives PanIN to PDAC progression in immortalized human pancreatic ductal cells. Conversely, depletion of USP21 impairs PDAC tumor growth. Mechanistically, USP21 deubiquitinates and stabilizes the TCF/LEF transcription factor TCF7, which promotes cancer cell stemness. Our work identifies and validates USP21 as a PDAC oncogene, providing a potential druggable target for this intractable disease.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Hou P,Ma X,Zhang Q,Wu CJ,Liao W,Li J,Wang H,Zhao J,Zhou X,Guan C,Ackroyd J,Jiang S,Zhang J,Spring DJ,Wang YA,DePinho RAdoi
10.1101/gad.326314.119subject
Has Abstractpub_date
2019-10-01 00:00:00pages
1361-1366issue
19-20eissn
0890-9369issn
1549-5477pii
gad.326314.119journal_volume
33pub_type
杂志文章abstract::Two retrovirus promoter trap vectors (U3His and U3Neo) have been used to disrupt genes expressed in totipotent murine embryonal stem (ES) cells. Selection in L-histidinol or G418 produced clones in which the coding sequences for histidinol-dehydrogenase or neomycin-phosphotransferase were fused to sequences in or near...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.6.919
更新日期:1992-06-01 00:00:00
abstract::Rosiglitazone (rosi) is a powerful insulin sensitizer, but serious toxicities have curtailed its widespread clinical use. Rosi functions as a high-affinity ligand for peroxisome proliferator-activated receptor γ (PPARγ), the adipocyte-predominant nuclear receptor (NR). The classic model, involving binding of ligand to...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.237628.114
更新日期:2014-05-01 00:00:00
abstract::Expression of the gene encoding atrial natriuretic factor (ANF) during mouse cardiac embryogenesis was studied using in situ hybridization to histologic sections. ANF mRNA was first detected in a subpopulation of myocardial cells at day 8 of embryogenesis. During day 9, abundant hybridization of the ANF probe to the a...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1.7.693
更新日期:1987-09-01 00:00:00
abstract::A long-standing model postulates that X-chromosome dosage compensation in Drosophila occurs by twofold up-regulation of the single male X, but previous data cannot exclude an alternative model, in which male autosomes are down-regulated to balance gene expression. To distinguish between the two models, we used RNA int...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1343705
更新日期:2005-10-01 00:00:00
abstract::We have investigated the role of erythroid Kruppel-like factor (EKLF) in expression of the human beta-globin genes in compound EKLF knockout/human beta-locus transgenic mice. EKLF affects only the adult mouse beta-globin genes in homozygous knockout mice; heterozygous mice are unaffected. Here we show that EKLF knocko...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.22.2894
更新日期:1996-11-15 00:00:00
abstract::The canoemisty1 (cnomis1) mutation was isolated by virtue of its severe rough eye phenotype from approximately 500 fly lines, each harboring a single autosomal insertion of a P element (Bm delta w). Excision of the P element generated a lethal, null allele, cnomis10, together with many revertants with normal eye morph...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.5.612
更新日期:1995-03-01 00:00:00
abstract::The timing of asexual fruiting body formation during Aspergillus nidulans colony development is precisely regulated so that conidiophores are typically produced 1-2 mm behind the growing edge of the colony. Mutations in any of four A. nidulans genes, flbB, flbC, flbD, or flbE, result in colonies that are delayed at le...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.9.4.491
更新日期:1995-02-15 00:00:00
abstract::The recombination site dif is the target on the Escherichia coli chromosome of the site-specific recombinases XerC and XerD. The dif/XerC-D system plays a role during the cell cycle, probably by favoring sister chromosome monomerization or separation. A phenomenon of regional control over dif activity, also analyzed i...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.10.9.1152
更新日期:1996-05-01 00:00:00
abstract::MicroRNAs (miRNAs) and transcription factors (TFs) are primary metazoan gene regulators. Whereas much attention has focused on finding the targets of both miRNAs and TFs, the transcriptional networks that regulate miRNA expression remain largely unexplored. Here, we present the first genome-scale Caenorhabditis elegan...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1678608
更新日期:2008-09-15 00:00:00
abstract::The essential splicing factor human UAP56 (hUAP56) is a DExD/H-box protein known to promote prespliceosome assembly. Here, using a series of hUAP56 mutants that are defective for ATP-binding, ATP hydrolysis, or dsRNA unwindase/helicase activity, we assess the relative contributions of these biochemical functions to pr...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1657308
更新日期:2008-07-01 00:00:00
abstract::Nonsense-mediated mRNA decay (NMD) is a quality control mechanism that detects and degrades mRNAs containing premature stop codons (PTCs). In vertebrates, PTCs trigger efficient NMD when located upstream of an exon junction complex (EJC). Degradation of PTC-containing mRNAs requires the endonucleolytic activity of SMG...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.604610
更新日期:2010-11-01 00:00:00
abstract::The neurofibromatosis type II (NF2) tumor suppressor encodes a putative cytoskeletal associated protein, the loss of which leads to the development of Schwann cell tumors associated with NF2 in humans. The NF2 protein merlin belongs to the band 4.1 family of proteins that link membrane proteins to the cytoskeleton and...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.10.1253
更新日期:1997-05-15 00:00:00
abstract::Plectin, a major linker and scaffolding protein of the cytoskeleton, has been shown to be essential for the mechanical integrity of skin, skeletal muscle, and heart. Studying fibroblast and astroglial cell cultures derived from plectin (-/-) mice, we found that their actin cytoskeleton, including focal adhesion contac...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.21.3442
更新日期:1998-11-01 00:00:00
abstract::We have studied the effect of exogenous expression of the basal transcription factor TFIID on the activities of several different TATA-containing and TATA-lacking promoters. Overexpression of TFIID from a transfected plasmid in Drosophila Schneider cells resulted in substantial concentration-dependent increases in exp...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.2.304
更新日期:1992-02-01 00:00:00
abstract::Medulloblastoma (MB) is the most common pediatric CNS malignancy. We identify EAG2 as an overexpressed potassium channel in MBs across different molecular and histological subgroups. EAG2 knockdown not only impairs MB cell growth in vitro, but also reduces tumor burden in vivo and enhances survival in xenograft studie...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.193789.112
更新日期:2012-08-15 00:00:00
abstract::The proteasome is well known for its regulation of the cell cycle and degradation of mis-folded proteins, yet many of its functions are still unknown. We show that RPN11, a gene encoding a subunit of the regulatory cap of the proteasome, is required for UV-stimulated activation of Gcn4p target genes, but is dispensabl...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.863801
更新日期:2001-01-15 00:00:00
abstract::Bistability in developmental pathways refers to the generation of binary outputs from graded or noisy inputs. Signaling thresholds are critical for bistability. Specification of the left/right (LR) axis in vertebrate embryos involves bistable expression of transforming growth factor beta (TGFbeta) member NODAL in the ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1682108
更新日期:2008-11-01 00:00:00
abstract::The transcription factor TFIIB plays a central role in preinitiation complex assembly, providing a bridge between promoter-bound TFIID and RNA Polymerase II. TFIIB possesses sequence-specific DNA-binding ability and interacts with the TFIIB-recognition element (BRE), present in many promoters. Here we show that the BR...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.206901
更新日期:2001-11-15 00:00:00
abstract::The Bloom's syndrome gene (BLM) plays a pivotal role in the maintenance of genomic stability in somatic cells. It encodes a DNA helicase (BLM) of the RecQ family, but the exact function of BLM remains elusive. To study this question, we have cloned the BLM homolog of the frog Xenopus laevis (xBLM) and have raised anti...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.822400
更新日期:2000-10-15 00:00:00
abstract::Caenorhabditis elegans let-7, a founding member of the microRNA family, is predicted to bind to six sites in the 3'UTR of the mRNA of its target gene, lin-41, to down-regulate LIN-41. Here, we demonstrate that wild-type let-7 microRNA binds in vitro to RNA from the lin-41 3'UTR. This interaction is dependent on two co...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1165404
更新日期:2004-01-15 00:00:00
abstract::Coliphage N4 is a double-stranded DNA virus that requires the sequential activity of three different RNA polymerases during infection. The N4 virion RNA polymerase, which is carried in the virion and is injected with the DNA at the start of infection, is responsible for the synthesis of N4 early RNAs. In vitro, the vi...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.10.2010
更新日期:1992-10-01 00:00:00
abstract::Expression of both N-myc and c-myc is induced rapidly and dramatically in normal pre-B cells after stimulation with interleukin-7 (IL-7), a pre-B cell-specific growth factor. These IL-7-induced increases in N-myc and c-myc expression are mediated at the transcriptional level; for N-myc, a major portion of the inductio...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.6.1.61
更新日期:1992-01-01 00:00:00
abstract::The assembly and disassembly of protein complexes at replication origins play a crucial role in the regulation of chromosomal DNA replication. The sequential binding of the origin recognition complex (ORC), Cdc6, and the minichromosome maintenance (MCM/P1) proteins produces a licensed replication origin. Before the in...
journal_title:Genes & development
pub_type: 杂志文章
doi:
更新日期:2000-06-15 00:00:00
abstract::Commitment to mitosis is regulated by a protein kinase complex called MPF. MPF is inhibited by Wee1-related kinases and activated by Cdc25 phosphatase. MPF activation further boosts Cdc25 and represses Wee1. This feedback control probably involves polo kinase. A dominant cut12.s11 mutation in the Schizosaccharomyces p...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.256003
更新日期:2003-06-15 00:00:00
abstract::In mitosis, the spindle checkpoint protein Mad2 averts aneuploidy by delaying anaphase onset until chromosomes align. Here we show that depletion of Mad2 in meiosis I mouse oocytes induced an increased incidence of aneuploidy. Proteolysis of cyclin B and securin commenced earlier in Mad2-depleted oocytes, resulting in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.328105
更新日期:2005-01-15 00:00:00
abstract::The Rbfox proteins (Rbfox1, Rbfox2, and Rbfox3) regulate the alternative splicing of many important neuronal transcripts and have been implicated in a variety of neurological disorders. However, their roles in brain development and function are not well understood, in part due to redundancy in their activities. Here w...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.182477.111
更新日期:2012-03-01 00:00:00
abstract::The rpoH gene of Escherichia coli encodes sigma 32, the 32-kD sigma-factor responsible for the heat-inducible transcription of the heat shock genes. rpoH is transcribed from at least three promoters. Two of these promoters are recognized by RNA polymerase containing sigma 70, the predominant sigma-factor. We purified ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.9.1462
更新日期:1989-09-01 00:00:00
abstract::The Komeda miniature rat Ishikawa (KMI) is a naturally occurring mutant caused by an autosomal recessive mutation mri, which exhibits longitudinal growth retardation. Here we identified the mri mutation as a deletion in the rat gene encoding cGMP-dependent protein kinase type II (cGKII). KMIs showed an expanded growth...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1224204
更新日期:2004-10-01 00:00:00
abstract::One of the first steps in neurogenesis is the diversification of cells along the dorsoventral axis. In Drosophila the central nervous system develops from three longitudinal columns of cells: ventral cells that express the vnd/nk2 homeobox gene, intermediate cells, and dorsal cells that express the msh homeobox gene. ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.22.3591
更新日期:1998-11-15 00:00:00
abstract::Gene silencing by double-stranded RNA is a widespread phenomenon called RNAi, involving homology-dependent degradation of mRNAs. Here we show that RNAi is established in the Drosophila female germ line. mRNA transcripts are translationally quiescent at the arrested oocyte stage and are insensitive to RNAi. Upon oocyte...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.990802
更新日期:2002-08-01 00:00:00