Abstract:
:The target gene(s) required for Myc-mediated tumorigenesis are still elusive. Here we show that while endogenous c-Myc is surprisingly dispensable for skin homeostasis and TPA-induced hyperplasia, c-Myc-deficient epidermis is resistant to Ras-mediated DMBA/TPAinduced tumorigenesis. This is mechanistically linked to p21(Cip1), which is induced in tumors by the activated Ras-ERK pathway but repressed by c-Myc. Acute elimination of c-Myc in established tumors leads to the up-regulation of p21(Cip1), and epidermis lacking both p21(Cip1) and c-Myc reacquires normal sensitivity to DMBA/TPA-induced tumorigenesis. This identifies c-Myc-mediated repression of p21(Cip1) as a key step for Ras-driven epidermal tumorigenesis.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Oskarsson T,Essers MA,Dubois N,Offner S,Dubey C,Roger C,Metzger D,Chambon P,Hummler E,Beard P,Trumpp Adoi
10.1101/gad.381206subject
Has Abstractpub_date
2006-08-01 00:00:00pages
2024-9issue
15eissn
0890-9369issn
1549-5477pii
20/15/2024journal_volume
20pub_type
杂志文章abstract::The YAP transcription coactivator has been implicated as an oncogene and is amplified in human cancers. Recent studies have established that YAP is phosphorylated and inhibited by the Hippo tumor suppressor pathway. Here we demonstrate that the TEAD family transcription factors are essential in mediating YAP-dependent...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1664408
更新日期:2008-07-15 00:00:00
abstract::Ecsit is a cytosolic adaptor protein essential for inflammatory response and embryonic development via the Toll-like and BMP (bone morphogenetic protein) signal transduction pathways, respectively. Here, we demonstrate a mitochondrial function for Ecsit (an evolutionary conserved signaling intermediate in Toll pathway...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.408407
更新日期:2007-03-01 00:00:00
abstract::Cell cycle transitions are often accompanied by the degradation of regulatory molecules. Targeting proteins to the proteasome for degradation is accomplished by the covalent addition of ubiquitin chains. The specificity of this pathway is largely dictated by a set of enzymes called ubiquitin ligases (or E3s). The anap...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1478306
更新日期:2006-11-15 00:00:00
abstract::Nonsense-mediated decay (NMD) is a translation-dependent RNA quality control mechanism that occurs in the cytoplasm. However, it is unknown how NMD regulates the stability of RNAs translated at the endoplasmic reticulum (ER). Here, we identify a localized NMD pathway dedicated to ER-translated mRNAs. We previously ide...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.338061.120
更新日期:2020-08-01 00:00:00
abstract::Ubiquitin-mediated proteolysis controls the abundance of many cell cycle regulatory proteins. Recent work in Saccharomyces cerevisiae suggests that a complex consisting of Cdc53, Skp1, and a third component known as an F-box protein (termed SCF) in combination with Cdc34 specifically targets regulatory proteins for de...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.12.16.2587
更新日期:1998-08-15 00:00:00
abstract::S-phase cyclin-dependent kinase Cdc28-Clb5 (CDK-S) and Dbf4-dependent kinase Cdc7-Dbf4 (DDK) are highly conserved kinases well known for their roles in the initiation of DNA replication. CDK-S is also essential for initiation of meiotic recombination because it phosphorylates Ser30 of Mer2, a meiosis-specific double-s...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1626408
更新日期:2008-02-01 00:00:00
abstract::The MMTVD/myc transgenic mice spontaneously develop oligoclonal CD4+CD8+ T-cell tumors. We used provirus insertional mutagenesis in these mice to identify putative collaborators of c-myc. We found that Notch1 was mutated in a high proportion (52%) of these tumors. Proviruses were inserted upstream of the exon coding f...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.15.1930
更新日期:1996-08-01 00:00:00
abstract::H4K20 methylation is a broad chromatin modification that has been linked with diverse epigenetic functions. Several enzymes target H4K20 methylation, consistent with distinct mono-, di-, and trimethylation states controlling different biological outputs. To analyze the roles of H4K20 methylation states, we generated c...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.476008
更新日期:2008-08-01 00:00:00
abstract::Sensory organ formation in Drosophila is activated by proneural genes that encode basic-helix-loop-helix (bHLH) transcription factors. These genes are antagonized by hairy and other proline-bHLH proteins. hairy has not been shown to bind to DNA and has been proposed to form inactive heterodimers with proneural activat...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.8.22.2743
更新日期:1994-11-15 00:00:00
abstract::The RNA polymerase II (RNAPII) C-terminal domain kinase, CDK12, regulates genome stability, expression of DNA repair genes, and cancer cell resistance to chemotherapy and immunotherapy. In addition to its role in mRNA biosynthesis of DNA repair genes, we show here that CDK12 phosphorylates the mRNA 5' cap-binding repr...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.322339.118
更新日期:2019-04-01 00:00:00
abstract::The SNF1 protein kinase is broadly conserved in eukaryotes and has been implicated in responses to environmental and nutritional stress. In yeast, the SNF1 kinase has a central role in the response to glucose starvation. SNF1 is associated with its activating subunit, SNF4, and other proteins in complexes. Using the t...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.10.24.3105
更新日期:1996-12-15 00:00:00
abstract::Thousands of eukaryotic protein-coding genes are noncanonically spliced to produce circular RNAs. Bioinformatics has indicated that long introns generally flank exons that circularize in Drosophila, but the underlying mechanisms by which these circular RNAs are generated are largely unknown. Here, using extensive muta...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.270421.115
更新日期:2015-10-15 00:00:00
abstract::We isolated a novel bHLH protein gene Mesp2 (for mesoderm posterior 2) that cross-hybridizes with Mesp1 expressed in the early mouse mesoderm. Mesp2 is expressed in the rostral presomitic mesoderm, but down-regulated immediately after the formation of the segmented somites. To determine the function of MesP2 protein (...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.11.14.1827
更新日期:1997-07-15 00:00:00
abstract::Activating JAK2 point mutations are implicated in the pathogenesis of myeloid and lymphoid malignancies, including high-risk B-cell acute lymphoblastic leukemia (B-ALL). In preclinical studies, treatment of JAK2 mutant leukemias with type I JAK2 inhibitors (e.g., Food and Drug Administration [FDA]-approved ruxolitinib...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.307504.117
更新日期:2018-06-01 00:00:00
abstract::To investigate the relationship between splicing and polyadenylation during the production of vertebrate mRNAs, we examined the effect of mutation of a poly(A) site on splicing of upstream introns. Mutation of the AAUAAA polyadenylation consensus sequence inhibited in vitro splicing of an upstream intron. The magnitud...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.5.11.2086
更新日期:1991-11-01 00:00:00
abstract::Cosuppression is a silencing phenomenon triggered by the introduction of homologous DNA sequences into the genomes of organisms as diverse as plants, fungi, flies, and nematodes. Here we report sex-induced silencing (SIS), which is triggered by tandem integration of a transgene array in the human fungal pathogen Crypt...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1970910
更新日期:2010-11-15 00:00:00
abstract::Sox10 is a high-mobility-group transcriptional regulator in early neural crest. Without Sox10, no glia develop throughout the peripheral nervous system. Here we show that Sox10 is restricted in the central nervous system to myelin-forming oligodendroglia. In Sox10-deficient mice progenitors develop, but terminal diffe...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.215802
更新日期:2002-01-15 00:00:00
abstract::In Drosophila, the development of the compound eye depends on the movement of a morphogenetic furrow (MF) from the posterior (P) to the anterior (A) of the eye imaginal disc. We define several subdomains along the A-P axis of the eye disc that express distinct combinations of transcription factors. One subdomain, ante...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1009002
更新日期:2002-09-15 00:00:00
abstract::The conserved RCN family of proteins can bind and directly regulate calcineurin, a Ca(2+)-activated protein phosphatase involved in immunity, heart growth, muscle development, learning, and other processes. Whereas high levels of RCNs can inhibit calcineurin signaling in fungal and animal cells, RCNs can also stimulat...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1159204
更新日期:2004-01-01 00:00:00
abstract::DNA methylation is a key regulator of embryonic stem cell (ESC) biology, dynamically changing between naïve, primed, and differentiated states. The p53 tumor suppressor is a pivotal guardian of genomic stability, but its contributions to epigenetic regulation and stem cell biology are less explored. We report that, in...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.299198.117
更新日期:2017-05-15 00:00:00
abstract::In many eukaryotes, siRNAs bound to Argonaute proteins guide chromatin-modifying enzymes to complementary loci, resulting in transcriptional gene silencing. Multiple lines of evidence indicate that siRNAs base-pair with longer RNAs produced at target loci, but the possibility that siRNAs base-pair directly with DNA re...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.294900.116
更新日期:2016-12-15 00:00:00
abstract::The embryonic ectoderm in Drosophila displays a highly organized arrangement of specific structures along the dorsal-ventral axis. To establish this characteristic design, cells must receive instructive cues regarding their position. We present evidence that during stages 8-9 of embryonic development, the Drosophila E...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.10.1937
更新日期:1993-10-01 00:00:00
abstract::In this issue of Genes & Development, Dowen and colleagues (pp. 1515-1528) elegantly unify two previously unconnected aspects of physiology. The investigators provide significant genetic evidence to support a critical link between developmental timing decisions and the regulation of lipid mobilization at the transitio...
journal_title:Genes & development
pub_type: 评论,杂志文章
doi:10.1101/gad.285460.116
更新日期:2016-07-01 00:00:00
abstract::Unrepaired DNA lesions in the template strand block the replication fork. In yeast, Mec1 protein kinase-mediated replication checkpoint prevents the breakdown of replication forks and maintains viability in DNA-damaged cells going through the S phase. By ensuring that the replisome does not dissociate from the fork st...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1793409
更新日期:2009-06-15 00:00:00
abstract::Numerous lines of study have suggested that the Hox genes, encoding putative transcription factors, are key genes in the establishment of the body plan of the mammalian embryo. To examine the role of Hoxa-5 (Hox1.3) gene during development, we have used targeted mutagenesis in embryonic stem cells to produce a strain ...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.11.2085
更新日期:1993-11-01 00:00:00
abstract::Extensive DNA elimination via a DNA breakage and rejoining process occurs during macronuclear development in the hypotrich ciliate Euplotes crassus. The excision process involves the removal of short, unique segments of DNA (internal eliminated sequences; IESs) and at least two highly repetitive families of transposon...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.1.84
更新日期:1993-01-01 00:00:00
abstract::The 134-bp enhancer region of the pancreatic elastase I gene is sufficient to direct pancreatic acinar cell-specific transcription in transgenic mice and in transfected cells in culture. Ten-base-pair scanner mutations in three separate enhancer domains that inactivate enhancer function in transfected pancreatic cells...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.3.5.687
更新日期:1989-05-01 00:00:00
abstract::Cohesin is a chromosome-associated multisubunit protein complex that is highly conserved in eukaryotes and has close homologs in bacteria. Cohesin mediates cohesion between replicated sister chromatids and is therefore essential for chromosome segregation in dividing cells. Cohesin is also required for efficient repai...
journal_title:Genes & development
pub_type: 杂志文章,评审
doi:10.1101/gad.1724308
更新日期:2008-11-15 00:00:00
abstract::Transformation of primary rodent cells by the adenovirus E1A and E1B oncogenes is a two-step process, where E1A-dependent induction of proliferation is coupled to E1B-dependent suppression of programmed cell death (apoptosis). The E1B gene encodes two distinct transforming proteins, the 19K and 55K proteins, both of w...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.7.4.546
更新日期:1993-04-01 00:00:00
abstract::The cJun N-terminal kinase 1 (JNK1) is implicated in diet-induced obesity. Indeed, germline ablation of the murine Jnk1 gene prevents diet-induced obesity. Here we demonstrate that selective deficiency of JNK1 in the murine nervous system is sufficient to suppress diet-induced obesity. The failure to increase body mas...
journal_title:Genes & development
pub_type: 杂志文章
doi:10.1101/gad.1878510
更新日期:2010-02-01 00:00:00