Abstract:
:There are at least three distinct MAP kinase signaling modules in mammalian cells, distinguished by the family of kinases (Erk, SAPK/JNK, or p38) that is ultimately activated. Many input signals activate multiple MAP kinase cascades, and the mechanisms that control the specificity of signal output are not well understood. We show that SEK1/MKK4, a MAP kinase kinase proposed to activate SAPK/JNK, is a very potent inhibitor of p54 SAPK beta/JNK3 both in vitro and in vivo if present at equimolar or higher ratios. In contrast SEK can activate SAPK when present in substoichiometric amounts, but this activation is slow, consistent with the rate-limiting step in activation being the dissociation of an inactive SEK:SAPK complex. The N-terminal unique region of SEK is both necessary and partially sufficient for inhibition of SAPK, and is also necessary for activation of SAPK by SEK in vitro. We have also used the p38 MAP kinase and its activator MKK6 to examine the regulatory relationships among different kinases involved in stress responses. We show using purified kinases that inhibitory activity is specific for the combination of SEK and SAPK: SEK can activate but not inhibit p38, and MKK6 can activate but not inhibit SAPK beta and p38. These results reveal a potential mechanism for regulating stress-activated kinases, adding to a growing body of evidence suggesting that MAP kinases are controlled by relatively stable interactions with their activators.
journal_name
Oncogenejournal_title
Oncogeneauthors
Kieran MW,Katz S,Vail B,Zon LI,Mayer BJdoi
10.1038/sj.onc.1203057subject
Has Abstractpub_date
1999-11-18 00:00:00pages
6647-57issue
48eissn
0950-9232issn
1476-5594journal_volume
18pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::Human hematopoietic progenitor cells (TF-1) undergo apoptosis upon deprivation of their dependent cytokine. In this report, we have isolated and characterized some spontaneously derived cytokine-independent variants from TF-1 cells. Analysis of several signaling molecules known to be activated by the GM-CSF pathway re...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1200884
更新日期:1997-02-13 00:00:00
abstract::MEK kinases (MEKKs) are serine-threonine kinases that regulate sequential protein phosphorylation pathways involving mitogen-activated protein kinases (MAPKs), including members of the Jun kinase (JNK) family. MEKK1 is a 196 kDa protein that when cleaved by caspase-3-like proteases generates an active COOH-terminal ki...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201421
更新日期:1997-11-13 00:00:00
abstract::Adenomatous polyposis coli (APC) gene mutations have been implicated in familial and sporadic gastrointestinal (GI) cancers. APC mutations are associated with autosomal dominant inheritance of disease in humans. Similarly, mice that contain a single mutant APC gene encoding a protein truncated at residue 716 (Apc(Δ716...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.633
更新日期:2011-06-09 00:00:00
abstract::Interstitial fluid flow in and around the tumor tissue is a physiologically relevant mechanical signal that regulates intracellular signaling pathways throughout the tumor. Yet, the effects of interstitial flow and associated fluid shear stress on the tumor cell function have been largely overlooked. Using in vitro bi...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.397
更新日期:2015-08-27 00:00:00
abstract::Although transforming ras oncogenes have been implicated as causative factors in liver cell transformation, the exact function and phenotypic alterations generated by the expression of such transforming genes in liver epithelial cells has yet to be defined. We have utilized a retroviral vector system to deliver an ind...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1988-09-01 00:00:00
abstract::In contrast to the hereditary form of medullary thyroid carcinoma (MTC), little is known about the etiology of sporadic MTC. Somatic gain-of-function mutations in the RET proto-oncogene, encoding a receptor tyrosine kinase, are found in an average of 40% of sporadic MTC. We analysed 31 sporadic MTC for somatic and ger...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204289
更新日期:2001-04-19 00:00:00
abstract::Chromosome 17 is one of the most frequently altered chromosomes in malignant breast cancer. At least four genes implicated in breast cancer reside on chromosome 17 (p53, 17p13; Her-2/neu/ERBB2, 17q12; BRCA1, 17q21; and nm23, 17q22). In addition, allelic imbalance has been described for at least five regions of chromos...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201073
更新日期:1997-05-15 00:00:00
abstract::Stimulator of interferon genes (STING) is a cellular sensor that controls cytosolic DNA-activated innate immune signaling. We have previously demonstrated that STING-deficient mice are resistant to carcinogen-induced skin cancer, similar to myeloid differentiation primary response gene 88 (MyD88) deficient mice, since...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.457
更新日期:2015-10-08 00:00:00
abstract::In this study, we examined the role of the E-cadherin-repressed gene human Nanos1 (hNanos1) in tumor invasion process. First, our in vivo study revealed that hNanos1 mRNAs were overexpressed in invasive lung carcinomas. Moreover, hNanos1 was co-localized with MT1-MMP (membrane type 1-matrix metalloproteinase) in E-cad...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1211035
更新日期:2008-06-12 00:00:00
abstract::Mitochondrial membrane permeabilization is a critical event in the process leading to physiological or chemotherapy-induced apoptosis. This permeabilization event is at least in part under the control of the permeability transition pore complex (PTPC), which interacts with oncoproteins from the Bcl-2 family as well as...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203299
更新日期:2000-01-13 00:00:00
abstract::The IGF2 gene, which encodes a growth factor, is subject to genomic imprinting. The frequently observed loss of IGF2 imprinting in a variety of tumors has been suggested to contribute to neoplasia. Since these reports have not documented the imprinting status of IGF2 at the cellular level, it cannot be excluded that t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201501
更新日期:1998-01-08 00:00:00
abstract::Rac1-GTPases serve as intermediary cellular switches, which conduct transient and constitutive signals from upstream cues, including those from Ras oncoproteins. Although the sirtuin1 (SIRT1) deacetylase is overexpressed in several human cancers and has recently been linked to cancer cell motility as a context-depende...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.549
更新日期:2015-01-08 00:00:00
abstract::MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression post-transcriptionally, are involved in many complex cellular processes. Several miRNAs are differentially expressed in hematopoietic tissues and play important roles in normal differentiation, but, when aberrantly regulated, contribute to the abn...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.398
更新日期:2013-08-01 00:00:00
abstract::The biological outcome of TMPRSS2:ERG chromosomal translocations in prostate cancer (PC) remains poorly understood. To address this, we compared the transcriptional effects of TMPRSS2:ERG expression in a transgenic mouse model with those of ERG knockdown in a TMPRSS2:ERG-positive PC cell line. This reveals that ERG re...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.308
更新日期:2015-07-01 00:00:00
abstract::As tumors grow and invade beyond their homeostatic limits, the tumor cells are subjected to insufficient nutrient and oxygen supplies because of excessive demand for nutrition and oxygen, and insufficient vascularization. We therefore hypothesized that tolerance to nutrient deprivation as well as angiogenesis may be c...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205737
更新日期:2002-09-05 00:00:00
abstract::Proliferating cell nuclear antigen (PCNA) plays an essential role in nucleic acid metabolism as a component of the replication and repair machinery. This toroidal-shaped protein encircles DNA and can slide bidirectionally along the duplex. One of the well-established functions for PCNA is its role as the processivity ...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1200886
更新日期:1997-02-13 00:00:00
abstract::Genetic and biochemical evidence suggest that conserved region 3 (CR3) of the adenovirus Ela polypeptide can provide two distinct and separable functions: an N-terminal transcriptional activation region and a C-terminal promoter targeting region. It is thought that the promoter targeting region of Ela CR3 interacts wi...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
abstract::We have characterized a novel chicken c-myb exon whose sequences are specifically expressed in thymic cells. In situ hybridization experiments indicate that this thymus-specific coding exon is localized on a small chromosome, distinct from the large acrocentric chromosome 3 on which we recently mapped the bulk of 15 e...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1991-04-01 00:00:00
abstract::Cancer cells can use a variety of metabolic substrates to fulfill the bioenergetic and biosynthetic needs of their oncogenic program. Besides bioenergetics, cancer cell metabolism also directly influences genetic, epigenetic and signaling events associated with tumor progression. Many cancer cells are addicted to glut...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.364
更新日期:2017-04-01 00:00:00
abstract::The viability of rat embryo cells immortalized by thermosensitive mutants of SV40 or polyoma Large T antigen is impaired at the non-permissive temperature thus demonstrating that the immortal phenotype is dominantly maintained by Large T antigens. We have observed that exposing these cells to the restrictive temperatu...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::The cdk2 gene has been identified as a human cdc2/CDC28-related gene that encodes a protein kinase essential for the G1/S transition in mammalian cells, but not for the G2/M transition, which requires Cdk1, another p34cdc2/CDC28 homolog. Novel potential functions of Cdk2 have been uncovered by using two potent and spe...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203103
更新日期:1999-12-09 00:00:00
abstract::To identify tyrosine kinases that may regulate regeneration of the mammalian intestinal epithelium, we amplified portions of the catalytic domains of protein kinases expressed in intestinal crypt cells, using the polymerase chain reaction technique with primers directed against two invariant amino acid sequence motifs...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-07-01 00:00:00
abstract::RNF8 is a ubiquitin ligase with a FHA domain near its N terminus, and a RING-finger domain at its C terminus, through which it recruits several ubiquitin-conjugating enzymes. In metazoans, only the mitotic checkpoint regulator CHFR shares this domain architecture. Here we show that RNF8 is a nuclear protein that follo...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1210782
更新日期:2008-02-28 00:00:00
abstract::Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer therapy because of its relative tumor selectivity. However, many cancers including pancreatic cancer remain resistant towards TRAIL. To develop TRAIL for cancer therapy of pancreatic carcinoma, it will therefore b...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209776
更新日期:2007-01-11 00:00:00
abstract::The NF-kappa B precursor p100 (lyt-10, p97, p98) generates after proteolytic processing a 52 kDa subunit, which can bind to kappa B-motifs. A deregulated form of the p100 gene, which is structurally altered by a t(10;14) translocation, has a potential oncogenic role in certain human B cell lymphomas. In this study p10...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-08-01 00:00:00
abstract::To appreciate the involvement of known or potential susceptibility genes in sporadic breast tumors, we have searched for chromosomal deletions by studying loss of heterozygosity (LOH) at 43 microsatellite (CA)n markers from human chromosomes 10, 11 and 17, in 115 unselected consecutive samples of breast carcinoma with...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1200818
更新日期:1997-01-23 00:00:00
abstract::Histone deacetylases (HDACs) catalyse the removal of acetyl groups from the N-terminal tails of histones. All known HDACs can be categorized into one of four classes (I-IV). The class III HDAC or silencing information regulator 2 (Sir2) family exhibits characteristics consistent with a distinctive role in regulation o...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1210617
更新日期:2007-08-13 00:00:00
abstract::Fas-associated death domain (FADD) is an adaptor protein recruiting complexes of caspase 8 to death ligand receptors to induce extrinsic apoptotic cell death in response to a TNF superfamily member. Although, formation of the complex of FADD and caspase 8 upon death stimuli has been studied in detail, posttranslationa...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-018-0323-z
更新日期:2018-09-01 00:00:00
abstract::Chromosomal aberrations are a hallmark of human cancers, with complex cytogenetic rearrangements leading to genetic changes permissive for cancer initiation and progression. Protection of Telomere 1 (POT1) is an essential component of the shelterin complex and functions to maintain chromosome stability by repressing t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.405
更新日期:2017-04-06 00:00:00
abstract::MEMO1 (mediator of ErbB2-driven cell motility 1) regulates HER2-dependent cell migration. Increased MEMO1 expression is associated with cancer aggressiveness. Here, we found that MEMO1 is also involved in breast carcinogenesis via regulating insulin-like growth factor-I receptor-dependent signaling events. We showed t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.327
更新日期:2013-06-27 00:00:00