Abstract：
:The p53 tumor suppressor is often disrupted in human cancers by the acquisition of missense mutations. We generated mice with a missense mutation at codon 172 that mimics the p53R175H hot spot mutation in human cancer. p53 homozygous mutant mice have unstable mutant p53 in normal cells and stabilize mutant p53 in some but not all tumors. To investigate the significance of these data, we examined the regulation of mutant p53 stability by Mdm2, an E3 ubiquitin ligase that targets p53 for degradation, and p16INK4a, a member of the Rb tumor suppressor pathway. Mice lacking Mdm2 or p16INK4a stabilized mutant p53, and revealed an earlier age of tumor onset than p53 mutant mice and a gain-of-function metastatic phenotype. Analysis of tumors from p53 homozygous mutant mice with stable p53 revealed defects in the Rb pathway. Additionally, ionizing radiation stabilizes wild-type and mutant p53. Thus, the stabilization of mutant p53 is not a given but it is a prerequisite for its gain-of-function phenotype. Since mutant p53 stability mimics that of wild-type p53, these data indicate that drugs aimed at activating wild-type p53 will also stabilize mutant p53 with dire consequences.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Terzian T,Suh YA,Iwakuma T,Post SM,Neumann M,Lang GA,Van Pelt CS,Lozano Gdoi
10.1101/gad.1662908subject
Has Abstractpub_date
2008-05-15 00:00:00pages
1337-44issue
10eissn
0890-9369issn
1549-5477journal_volume
22pub_type
杂志文章abstract：:A novel histone methyltransferase, termed Set9, was isolated from human cells. Set9 contains a SET domain, but lacks the pre- and post-SET domains. Set9 methylates specifically lysine 4 (K4) of histone H3 (H3-K4) and potentiates transcription activation. The histone H3 tail interacts specifically with the histone deac...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.967202
更新日期：2002-02-15 00:00:00
abstract：:The LIM motif defines a double zinc finger structure found in proteins involved in cell fate determination and growth control. LIM proteins, which include LIM homeo domain, LIM kinase, focal adhesion, and LIM-only proteins, usually contain two or more LIM motifs clustered at their amino- or carboxy-terminal end. At pr...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.10.3.289
更新日期：1996-02-01 00:00:00
abstract：:In Xenopus embryos, a dorsal-ventral patterning gradient is generated by diffusing Chordin/bone morphogenetic protein (BMP) complexes cleaved by BMP1/Tolloid metalloproteinases in the ventral side. We developed a new BMP1/Tolloid assay using a fluorogenic Chordin peptide substrate and identified an unexpected negative...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1839309
更新日期：2009-11-01 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：:Actin is associated with all three nuclear RNA polymerases and acts in concert with nuclear myosin I (NM1) to drive transcription. Practically nothing is known regarding the state of actin and the functional interplay of actin and NM1 in transcription. Here we show that actin and NM1 act in concert to promote RNA poly...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.455908
更新日期：2008-02-01 00:00:00
abstract：:The crucifer Arabidopsis thaliana has been used widely as a model organism for the study of plant development. We describe here the development of an efficient insertional mutagenesis system in Arabidopsis that permits identification of genes by their patterns of expression during development. Transposable elements of...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.9.14.1797
更新日期：1995-07-15 00:00:00
abstract：:The chromo domain was identified as a homologous protein motif between Polycomb (Pc)--a member of the Pc-group genes encoding transcriptional repressors of the homeotic genes--and HP1--a heterochromatin-associated protein encoded by the suppressor of position effect variegation gene Su(var)205. Together with previous ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.6.7.1241
更新日期：1992-07-01 00:00:00
abstract：:Metazoans start embryogenesis with a relatively naïve genome. The transcriptionally inert, late-replicating heterochromatic regions, including the constitutive heterochromatin on repetitive sequences near centromeres and telomeres, need to be re-established during development. To explore the events initiating heteroch...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.272237.115
更新日期：2016-03-01 00:00:00
abstract：:Eukaryotic RNAs with premature termination codons (PTCs) are eliminated by nonsense-mediated decay (NMD). While human nonsense RNA degradation can be initiated either by an endonucleolytic cleavage event near the PTC or through decapping, the individual contribution of these activities on endogenous substrates has rem...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.246538.114
更新日期：2014-11-15 00:00:00
abstract：:Chromatin-modifying enzymes are known to be critical components for the correct differentiation of embryonic stem cells into specific lineages, such as neurons. Recently, the role of Polycomb group proteins has been studied in the specification and differentiation of muscle stem cells. In this perspective, we review a...
journal_title：Genes & development
pub_type： 评论,杂志文章
doi：10.1101/gad.2054311
更新日期：2011-05-15 00:00:00
abstract：:Calcineurin, a conserved Ca(2+)/calmodulin-regulated protein phosphatase, plays a crucial role in Ca(2+) signaling in a wide variety of cell types. In Saccharomyces cerevisiae, calcineurin positively regulates transcription in response to stress by dephosphorylating the transcription factor Crz1p/Tcn1p. Dephosphorylat...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.967602
更新日期：2002-03-01 00:00:00
abstract：:Children with trisomy 21/Down syndrome (DS) are at high risk to develop acute megakaryoblastic leukemia (DS-AMKL) and the related transient leukemia (DS-TL). The factors on human chromosome 21 (Hsa21) that confer this predisposing effect, especially in synergy with consistently mutated transcription factor GATA1 (GATA...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1856210
更新日期：2010-03-01 00:00:00
abstract：:We report on the function of the human ortholog of Saccharomyces cerevisiae Rif1 (Rap1-interacting factor 1). Yeast Rif1 associates with telomeres and regulates their length. In contrast, human Rif1 did not accumulate at functional telomeres, but localized to dysfunctional telomeres and to telomeric DNA clusters in AL...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1216004
更新日期：2004-09-01 00:00:00
abstract：:Morphogenesis of the insect kidney, the Malpighian tubules, is controlled in Drosophila by a single large cell, the tip cell. It has been postulated that this cell sends out a mitogenic signal that induces the division of neighboring cells. The signal and the molecules that receive it have remained elusive. We show th...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.12.12.1781
更新日期：1998-06-15 00:00:00
abstract：:We describe here a new murine homeo box gene, denoted Hlx, which is expressed within specific hematopoietic lineages. The cDNA sequence indicates that Hlx differs markedly from known vertebrate homeo box genes, and linkage analysis of an interspecific murine backcross showed that it resides at a novel homeo box locus ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.5.4.509
更新日期：1991-04-01 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：:Calcineurin, a Ca2+/calmodulin dependent protein phosphatase, regulates Ca2+-dependent processes in a wide variety of cells. In the yeast, Saccharomyces cerevisiae, calcineurin effects Ca2+-dependent changes in gene expression through regulation of the Crz1p transcription factor. We show here that calcineurin dephosph...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.13.7.798
更新日期：1999-04-01 00:00:00
abstract：:The senescence-associated secretory phenotype (SASP) is a major trait of senescent cells, but the molecular regulators of SASP factor secretion are poorly understood. Mass spectrometry analysis revealed that secretory carrier membrane protein 4 (SCAMP4) levels were strikingly elevated on the surface of senescent cells...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.313270.118
更新日期：2018-07-01 00:00:00
abstract：:Directed cell motility is at the basis of biological phenomena such as development, wound healing, and metastasis. It has been shown that substrate attachments mediate motility by coupling the cell's cytoskeleton with force generation. However, it has been unclear how the persistence of cell directionality is facilita...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.190413.112
更新日期：2012-09-01 00:00:00
abstract：:The Wnt pathway controls numerous developmental processes via the beta-catenin-TCF/LEF transcription complex. Deregulation of the pathway results in the aberrant accumulation of beta-catenin in the nucleus, often leading to cancer. Normally, cytoplasmic beta-catenin associates with APC and axin and is continuously pho...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.230302
更新日期：2002-05-01 00:00:00
abstract：:Dosage compensation in Drosophila occurs by a twofold increase in transcription per copy of X-linked genes in males (XY) compared with females (XX). msl-1 is one of four genes that are essential for dosage compensation in males, and MSL-1 protein is associated specifically with the male X chromosome. To explore the ba...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.8.6.698
更新日期：1994-03-15 00:00:00
abstract：:Cellular morphology is an essential determinant of cellular function in all kingdoms of life, yet little is known about how cell shape is controlled. Here we describe a molecular program that controls the early morphology of neurons through a metazoan-specific zinc finger protein, Unkempt. Depletion of Unkempt in mous...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.258483.115
更新日期：2015-03-01 00:00:00
abstract：:Upon activation by far-red light, phytochrome A signals are transduced through several pathways to promote photomorphogenesis. The COP1 E3 ligase represses photomorphogenesis in part by targeting transcription activators such as LAF1 and HY5 for destruction. Another positive regulator of photomorphogenesis is HFR1, a ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1247205
更新日期：2005-03-01 00:00:00
abstract：:The bcl-6 proto-oncogene encodes a POZ/zinc finger transcriptional repressor expressed in germinal center (GC) B and T cells and required for GC formation and antibody affinity maturation. Deregulation of bcl-6 expression by chromosomal rearrangements and point mutations of the bcl-6 promoter region are implicated in ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.12.13.1953
更新日期：1998-07-01 00:00:00
abstract：:Transabdominal (Tab), a dominant mutation in the Bithorax Complex (BX-C) of Drosophila, creates a sexually dimorphic pattern of segmental transformation that has complete penetrance and expressivity. Specific regions within the notum of the second thoracic segment (T2) are transformed into abdominal-like cuticle; thus...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.1.2.111
更新日期：1987-04-01 00:00:00
abstract：:The Hedgehog (Hh) family of secreted proteins controls many aspects of animal development. In Drosophila, Hh transduces its signal via Cubitus interruptus (Ci), a transcription factor present in two forms: a full-length activator and a carboxy-terminally truncated repressor that is derived from the full-length form by...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.13.21.2828
更新日期：1999-11-01 00:00:00
abstract：:Cellular senescence limits proliferation of potentially detrimental cells, preventing tumorigenesis and restricting tissue damage. However, the function of senescence in nonpathological conditions is unknown. We found that the human placental syncytiotrophoblast exhibited the phenotype and expressed molecular markers ...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.227512.113
更新日期：2013-11-01 00:00:00
abstract：:MicroRNAs are important regulators in many cellular processes, including stem cell self-renewal. Recent studies demonstrated their function as pluripotency factors with the capacity for somatic cell reprogramming. However, their role in human embryonic stem (ES) cells (hESCs) remains poorly understood, partially due t...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.17221311
更新日期：2011-10-15 00:00:00
abstract：:DinI is a recently described negative regulator of the SOS response in Escherichia coli. Here we show that it physically interacts with RecA and prevents the binding of single-stranded DNA to RecA, which is required for the activation of the latter. DinI also displaces ssDNA from a stable RecA-DNA cofilament, thus eli...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.862901
更新日期：2001-02-15 00:00:00
abstract：:Over a period of many months, Xenopus oocytes stockpile large quantities of tRNA for use during the first few hours of embryogenesis. To test the idea that these tRNAs are transcribed from one set of genes and that another set is used by somatic cells, we used synthetic oligonucleotides to analyze the sequence and ste...
journal_title：Genes & development
pub_type： 杂志文章
doi：10.1101/gad.3.8.1190
更新日期：1989-08-01 00:00:00
