Abstract:
:Loss of p53 sensitizes to antimicrotubule agents in human tumor cells, but little is known about its role during mitosis. We have identified the Polo-like kinase family member serum inducible kinase (Snk/Plk2) as a novel p53 target gene. Snk/Plk2 mutagenesis demonstrated that its kinase activity is negatively regulated by its C terminus. Small interfering RNA (siRNA)-mediated Snk/Plk2 silencing in the presence of the mitotic poisons paclitaxel (Taxol) or nocodazole significantly increased apoptosis, similar to p53 mutations, which confer paclitaxel sensitivity. Furthermore, we have demonstrated that the apoptosis due to silencing of Snk/Plk2 in the face of spindle damage occurs in mitotic cells and not in cells that have progressed to a G(1)-like state without dividing. Since siRNA directed against Snk/Plk2 promoted death of paclitaxel-treated cells in mitosis, we envision a mitotic checkpoint wherein p53-dependent activation of Snk/Plk2 prevents mitotic catastrophe following spindle damage. Finally, these studies suggest that disruption of Snk/Plk2 may be of therapeutic value in sensitizing paclitaxel-resistant tumors.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Burns TF,Fei P,Scata KA,Dicker DT,El-Deiry WSdoi
10.1128/mcb.23.16.5556-5571.2003subject
Has Abstractpub_date
2003-08-01 00:00:00pages
5556-71issue
16eissn
0270-7306issn
1098-5549journal_volume
23pub_type
杂志文章abstract::Keap1 regulates Nrf2 activity in response to xenobiotic and oxidative stresses. Nrf2 is an essential regulator of cytoprotective genes. Keap1-null mice are lethal by weaning age due to malnutrition caused by severe hyperkeratosis of the upper digestive tract. Analysis of Keap1::Nrf2 double mutant mice revealed that cu...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01591-09
更新日期:2010-06-01 00:00:00
abstract::The Saccharomyces cerevisiae CDC25 gene and closely homologous genes in other eukaryotes encode guanine nucleotide exchange factors for Ras proteins. We have determined the minimal region of the budding yeast CDC25 gene capable of activity in vivo. The region required for full biological activity is approximately 450 ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.3.1345
更新日期:1993-03-01 00:00:00
abstract::Following a proliferative phase of variable duration, most normal somatic cells enter a growth arrest state known as replicative senescence. In addition to telomere shortening, a variety of environmental insults and signaling imbalances can elicit phenotypes closely resembling senescence. We used p53(-/-) and p21(-/-)...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.20.6748-6757.2001
更新日期:2001-10-01 00:00:00
abstract::Mitotic chromosome condensation is chiefly driven by the condensin complex. The specific recognition (targeting) of chromosomal sites by condensin is an important component of its in vivo activity. We previously identified the rRNA gene cluster in Saccharomyces cerevisiae as an important condensin-binding site, but bo...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.16.7216-7225.2005
更新日期:2005-08-01 00:00:00
abstract::B52, an essential SR protein of Drosophila melanogaster, stimulates pre-mRNA splicing in splicing-deficient mammalian S100 extracts. Surprisingly, mutant larvae depleted of B52 were found to be capable of splicing at least several pre-mRNAs tested (H. Z. Ring and J. T. Lis, Mol. Cell. Biol. 14:7499-7506, 1994). In a h...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.20.1.181-186.2000
更新日期:2000-01-01 00:00:00
abstract::Plasmid DNA substrates were X-irradiated and injected into the nuclei of Xenopus laevis oocytes. After incubation for 20 h, DNA was recovered from the oocytes and analyzed simultaneously for repair and for intermolecular homologous recombination by electrophoresis and bacterial transformation. Oocyte-mediated repair o...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.11.5849
更新日期:1990-11-01 00:00:00
abstract::Tmprss2 encodes an androgen-regulated type II transmembrane serine protease (TTSP) expressed highly in normal prostate epithelium and has been implicated in prostate carcinogenesis. Although in vitro studies suggest protease-activated receptor 2 may be a substrate for TMPRSS2, the in vivo biological activities of TMPR...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.26.3.965-975.2006
更新日期:2006-02-01 00:00:00
abstract::The spliceosomal small nuclear RNAs U1, U2, U4, and U5 are transcribed by RNA polymerase II as precursors with extensions at their 3' ends. The 3' processing of these pre-snRNAs is not understood in detail. Two pathways of pre-U2 RNA 3' processing in vitro were revealed in the present investigation by using a series o...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.12.7178
更新日期:1997-12-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.5.2238
更新日期:1996-05-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00053-16
更新日期:2016-07-14 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.18.5.2712
更新日期:1998-05-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.24.9.3860-3873.2004
更新日期:2004-05-01 00:00:00
abstract::We have examined the in vivo sites of action for topoisomerases II in the 87A7 heat shock locus as a function of gene activity. When the hsp70 genes are induced, there is a dramatic redistribution of topoisomerase II in the locus which parallels many of the observed alterations in chromatin structure. In addition to c...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.13.12.7522
更新日期:1993-12-01 00:00:00
abstract::We describe a two-step strategy to alter any mouse locus repeatedly and efficiently by direct positive selection. Using conventional targeting for the first step, a functional neo gene and a nonfunctional HPRT minigene (the "socket") are introduced into the genome of HPRT- embryonic stem (ES) cells close to the chosen...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.10.6936
更新日期:1994-10-01 00:00:00
abstract::To determine if Neu is dominant over transforming growth factor beta (TGF-beta), we crossed mouse mammary tumor virus (MMTV)-Neu mice with MMTV-TGF-beta1(S223/225) mice expressing active TGF-beta1 in the mammary gland. Bigenic (NT) and Neu-induced mammary tumors developed with a similar latency. The bigenic tumors and...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.23.8691-8703.2003
更新日期:2003-12-01 00:00:00
abstract::Microinjection of p21Ha-ras proteins into Xenopus laevis oocytes induces a rapid increase of 1,2-diacylglycerol (DAG) levels. The observed alterations in DAG levels were consistent with the ability of the protein to induce maturation, measured by germinal vesicle breakdown (GVBD). Both the increase in DAG levels and G...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.1.333
更新日期:1990-01-01 00:00:00
abstract::After flagellar detachment in Chlamydomonas reinhardi, there is a rapid synthesis and accumulation of mRNAs for tubulin and other flagellar proteins. Maximum levels of these mRNAs (flagellar RNAs) are reached within 1 h after deflagellation, after which they are rapidly degraded to their predeflagellation levels. The ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.1.54
更新日期:1986-01-01 00:00:00
abstract::We used a transient-expression assay to identify two estrogen response elements (EREs) associated with the major chicken vitellogenin gene (VTGII). Each element was characterized by its ability to confer estrogen responsiveness when cloned in either orientation next to a chimeric reporter gene consisting of the herpes...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.3.1123
更新日期:1988-03-01 00:00:00
abstract::The LINE-1, or L1, family of interspersed repeated DNA constitutes roughly 10% of the mammalian genome. Its abundance is due to duplicative transposition via an RNA intermediate, L1-encoded proteins, and reverse transcription. Although, in principle, transposition may occur in any cell type, expression and transpositi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.4.2584
更新日期:1994-04-01 00:00:00
abstract::In Saccharomyces cerevisiae, a phosphorelay signal transduction pathway composed of Sln1p, Ypd1p, and Ssk1p, which are homologous to bacterial two-component signal transducers, is involved in the osmosensing mechanism. In response to high osmolarity, the phosphorelay system is inactivated and Ssk1p remains unphosphory...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.23.18.6662-6671.2003
更新日期:2003-09-01 00:00:00
abstract::DNA in the polyploid macronucleus of the ciliated protozoan Tetrahymena thermophila contains the modified base N6-methyladenine. We identified two GATC sites which are methylated in most or all of the 45 copies of the macronuclear genome. One site is 2 kilobases 5' to the histone H4-I gene, and the other is 5 kilobase...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.7.2364
更新日期:1986-07-01 00:00:00
abstract::We have previously described an isolated kinetoplast system from Crithidia fasciculata capable of ATP-dependent replication of kinetoplast DNA minicircles (L. Birkenmeyer and D.S. Ray, J. Biol. Chem. 261: 2362-2368, 1986). We present here the identification of two new minicircle species observed in short pulse-labelin...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.1.169
更新日期:1989-01-01 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::We set up an alternative splicing system in vitro in which the relative amounts of two spliced RNAs, one containing and the other lacking a particular exon, were directly proportional to the length of an inverted repeat inserted into the flanking introns. We then used the system to measure the effect of intramolecular...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.9.3194
更新日期:1987-09-01 00:00:00
abstract::The strength and duration of mitogen-activated protein kinase (MAPK) signaling have been shown to regulate cell fate in different cell types. In this study, a general mechanism is described that explains how subtle differences in signaling kinetics are translated into a specific biological outcome. In fibroblasts, the...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.24.1.144-153.2004
更新日期:2004-01-01 00:00:00
abstract::Quiescent mouse NIH 3T3 cells responded to microinjection of activated ras p21 with a rapid and sustained rise in intracellular pH (approximately 0.17 pH units). The p21-induced pH change was inhibited by amiloride treatment or growth of cells in medium low in sodium, suggesting a role for the Na+/H+ antiporter. Amilo...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.7.5.1984
更新日期:1987-05-01 00:00:00
abstract::Transcriptional silencing in Saccharomyces cerevisiae occurs at specific loci and is mediated by a multiprotein complex that includes Rap1p and the Sir proteins. We studied the function of a recently identified gene, DOT4, that disrupts silencing when overexpressed. DOT4 encodes an ubiquitin processing protease (hydro...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.10.6608
更新日期:1999-10-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00642-17
更新日期:2018-03-15 00:00:00
abstract::Reduction of the survival of motor neurons (SMN) protein levels causes the motor neuron degenerative disease spinal muscular atrophy, the severity of which correlates with the extent of reduction in SMN. SMN, together with Gemins 2 to 7, forms a complex that functions in the assembly of small nuclear ribonucleoprotein...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.13.5543-5551.2005
更新日期:2005-07-01 00:00:00
abstract::Five mouse alpha-tubulin isotypes are described, each distinguished by the presence of unique amino acid substitutions within the coding region. Most, though not all of these isotype-specific amino acids, are clustered at the carboxy terminus. One of the alpha-tubulin isotypes described is expressed exclusively in tes...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.7.2409
更新日期:1986-07-01 00:00:00