Abstract:
:Prostate cancer (PCa) cell proliferation is dependent on activation of the androgen receptor (AR), a ligand-dependent transcription factor. AR activation controls G1-S phase progression through fostering enhanced translation of the D-type cyclins, which promote cell cycle progression through activation of CDK4/6. However, the D-type cyclins harbor additional, CDK4/6 kinase-independent, functions through manipulation of transcription factors, including AR. It was previously established that cyclins D1 and D3 have the potential to modulate AR, and with regard to cyclin D1, disruption of this function occurs in human tumors. Therefore, it was essential to interrogate cyclin D3 function in this tumor type. Here, we show that cyclin D3 is found in association with AR in PCa cells, as mediated through a conserved motif. Cyclin D3 functions to attenuate AR activity through defined mechanisms that include modulation of ligand-dependent conformational changes and modulation of chromatin binding activity. Accumulated cyclin D3 slows cell proliferation in AR-dependent cells, thus suggesting that androgen-induced D-type cyclin production serves to temper the mitogenic response to androgen. Supporting this hypothesis, it is shown that cyclin D3 expression is reduced in primary PCas as a function of tumor grade, and inversely correlates with the proliferative index. In total, these data identify cyclin D3 as a critical modulator of the androgen response, whose deregulation may foster unchecked AR activity in PCa.
journal_name
Oncogenejournal_title
Oncogeneauthors
Olshavsky NA,Groh EM,Comstock CE,Morey LM,Wang Y,Revelo MP,Burd C,Meller J,Knudsen KEdoi
10.1038/sj.onc.1210981subject
Has Abstractpub_date
2008-05-15 00:00:00pages
3111-21issue
22eissn
0950-9232issn
1476-5594pii
1210981journal_volume
27pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::The introduction of new therapies against particular genetic mutations in non-small-cell lung cancer is a promising avenue for improving patient survival, but the target population is small. There is a need to discover new potential actionable genetic lesions, to which end, non-conventional cancer pathways, such as RN...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.469
更新日期:2016-08-18 00:00:00
abstract::Tumors consistently mimic wound-generating chronic inflammation; however, why they do not heal like wounds with fibrotic scars remains unknown. The components of the tumor microenvironment, such as transforming growth factor β (TGF-β) and fibroblast growth factors (FGFs), may account for this phenomenon. Tumor formati...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.512
更新日期:2017-07-06 00:00:00
abstract::The oligomerization chain reaction (OCR) strategy is a recently described technique for inactivation of target proteins that function as homoassociate complexes. This novel strategy is based on the fusion of self-associating coiled-coil (CC) domain of the nuclear factor promyelocytic leukemia (PML) to target proteins....
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206785
更新日期:2003-07-31 00:00:00
abstract::Tumor suppressor p53 functions are downregulated in most cervical cancers, because the product of human papilloma virus (HPV) oncogene E6 binds to and inactivates p53 by promoting its degradation. p73, a p53 homologue, is similar to p53 in structure and function but yet not degraded by HPV E6 gene product. In this stu...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206908
更新日期:2003-11-20 00:00:00
abstract::Raf-1 is a serine-threonine protein kinase that functions as a central component of the mitogen-activated protein kinase signal transduction pathway. Raf-1 activity is currently assayed in vitro by either measuring 32P incorporation into MEK, Raf-1's only characterized substrate, or by using the phosphorylated MEK to ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203862
更新日期:2000-10-12 00:00:00
abstract::Cellular senescence functions as a tumor suppressor that protects against cancer progression. α-Catulin, an α-catenin-related protein, is reported to have tumorigenic potential because it regulates the nuclear factor-κB (NF-κB) pathway, but little is known about its clinical relevance and the mechanism through which i...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.637
更新日期:2011-06-09 00:00:00
abstract::Melanoma-associated antigen A1 (MAGEA1) is member of the MAGE gene family that is expressed in male germ line cells and placenta under normal physiological conditions. Although MAGEA1's expression levels have been evaluated as one of the cancer testis (CT) antigens for immunotherapy in melanoma and several other cance...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2017.131
更新日期:2017-08-31 00:00:00
abstract::The human trk oncogene (originally identified in a colon carcinoma) was activated by a genetic rearrangement which resulted in replacement of the extracellular ligand-binding domain of the proto-trk transmembrane receptor by non-muscle tropomyosin sequences. The product of the trk oncogene, a protein of 70 kDa (p70trk...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1991-12-01 00:00:00
abstract::There is now much evidence to suggest that the p53 tumour suppressor protein functions to monitor the integrity of the genome. When DNA damage is detected, p53 suppresses cell growth to allow repair or directs the cell into apoptosis. The mechanism of action of p53 is as yet unclear but recent evidence has accumulated...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-10-05 00:00:00
abstract::The oncoprotein c-Myc contains two dimerization motifs- the helix-loop-helix (HLH) and the leucine zipper (LZ) - through which c-Myc specifically dimerizes with Max. We substituted regions of the c-Myc HLH and LZ motifs with the corresponding regions of structurally related proteins that do not interact with Max. Spec...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::The myb proto oncogene product (c-Myb) is a transcriptional regulator and its expression and function are tightly linked to the cellular entry into S phase and DNA synthesis. It has been shown [Venturelli, D., Travali, S. & Calabretta, B. (1990). Proc. Natl. Acad. Sci. USA, 87, 5963-5967] that inhibition of T-cell pro...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-10-01 00:00:00
abstract::We have optimized the conditions for efficient NIH3T3 focus formation by calcium phosphate transfection of proviral Abelson-murine leukemia virus (A-MuLV) plasmid DNA. Linearized pA-MuLV, P120 or P160 strains, when transfected with calf thymus carrier DNA, will produce 40-50 foci/100 ng pA-MuLV without co-transfecting...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1989-11-01 00:00:00
abstract::H1 histamine receptor (H1HR) belongs to the family of rhodopsin-like G-protein-coupled receptors. Recent studies have shown that H1HR expression is increased in several types of cancer. However, its functional roles in tumor progression remain largely unknown, especially in hepatocellular carcinoma (HCC). We found tha...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/s41388-019-1093-y
更新日期:2020-02-01 00:00:00
abstract::Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are extracellular lipid mediators that signal through distinct members of the Edg/LP subfamily of G protein-coupled receptors (GPCRs). LPA and S1P receptors are expressed in almost every cell type and can couple to multiple G proteins (G(i), G(q) and G(12/1...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1204187
更新日期:2001-03-26 00:00:00
abstract::Checkpoint kinase 2 (Chk2) is known to mediate diverse cellular responses to genotoxic stress. The fundamental role of Chk2 is to regulate the network of genome-surveillance pathways that coordinate cell-cycle progression with DNA repair and cell survival or death. Defects in Chk2 contribute to the development of both...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209059
更新日期:2006-01-19 00:00:00
abstract::The Kelch-like ECH-associated protein 1 (KEAP1)-nuclear factor E2-related factor 2 (NRF2)pathway has a central role in cellular antioxidant defense. NRF2 activation due to KEAP1 or NRF2 mutations occurs frequently in many cancers, suggesting that NRF2 inhibition could be a promising therapeutic strategy. However, no p...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2017.153
更新日期:2017-09-14 00:00:00
abstract::Ras-genes encode for proteins important for transmitting extracellular signals from the cytoplasm to the nucleus. In this study we investigated the impact of Ras on cell cycle progression after hepatectomy by using adenoviral vectors (adv) expressing beta-galactosidase (beta-gal), a dominant-negative (Ras N17) or a do...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204690
更新日期:2001-08-30 00:00:00
abstract::Induction of apoptosis in tumor cells is an important mechanism of chemotherapy-induced cell death. The tumor-suppressor gene p53 is required for the efficient activation of apoptosis following chemotherapy. However, the molecular mechanism regulating p53-associated apoptosis remains controversial. In this study, we s...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-05-18 00:00:00
abstract::Bcl-2 is a key inhibitor of a broad range of apoptotic pathways, yet neither the mechanism of action nor the role of Bcl-2 subcellular localization are well understood. The subcellular localization of Bcl-2 includes the mitochondrial membrane as well as the contiguous membrane of the endoplasmic reticulum and nuclear ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202716
更新日期:1999-06-10 00:00:00
abstract::The forkhead transcription factor FOXM1 has a key role in DNA damage response, and its deregulated overexpression is associated with genotoxic drug resistance in breast cancer. However, little is known about the posttranslational mechanisms by which FOXM1 expression is regulated by genotoxic agents and how they are de...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.208
更新日期:2016-03-17 00:00:00
abstract::Phosphorylation of linker histone H1(S)-3 (previously named H1b) and core histone H3 is elevated in mouse fibroblasts transformed with oncogenes or constitutively active mitogen-activated protein kinase (MAPK) kinase (MEK). H1(S)-3 phosphorylation is the only histone modification known to be dependent upon transcripti...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206029
更新日期:2002-12-05 00:00:00
abstract::We have analysed the importance of proper substrate methylation by S-adenosylmethionine-dependent methyltransferases for cell survival and cell cycle progression. We show that treatment of cells with the methyltransferase inhibitor adenosine dialdehyde (AdOx) causes cell cycle arrest and death in different cell types....
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208855
更新日期:2005-10-27 00:00:00
abstract::The c-myc proto-oncogene has been shown to cause blockages to differentiation in many cell lineages. Although the mechanism by which c-Myc affects this process remains unknown, it is considered that it might result indirectly as an outcome of the continued cell-cycle progression invoked by c-Myc in cells which must gr...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201124
更新日期:1997-06-12 00:00:00
abstract::Rad54 and Mus81 mammalian proteins physically interact and are important for the homologous recombination DNA repair pathway; however, their functional interactions in vivo are poorly defined. Here, we show that combinatorial loss of Rad54 and Mus81 results in hypersensitivity to DNA-damaging agents, defects on both t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.16
更新日期:2016-09-15 00:00:00
abstract::Wild-type p53 protein displays a spectrum of activities including the ability to suppress transformed cell growth to direct apoptotic cell death and to mediate G1 checkpoint in response to cellular DNA damage. Earlier work showed that a self-association defective p53 protein retained transformation suppressor activity...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1996-08-01 00:00:00
abstract::Enhancer of Zeste homologue 2 (EZH2) belongs to the polycomb repressive complex 2 and catalyzes the methylation of histone H3 lysine 27. These pivotal epigenetic marks are altered in many cancers, including melanoma, as a result of EZH2 overexpression. Here, we show that the non-canonical-NF-kB pathway accounts for mo...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2015.331
更新日期:2016-05-01 00:00:00
abstract::Radicicol, a macrocyclic anti-fungal antibiotic, has the ability to suppress transformation by diverse oncogenes such as Src, Ras and Mos. Despite this useful property, the mechanism by which radicicol exerts its anti-transformation effects is currently unknown. To understand the transformation-suppressing effects of ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1201790
更新日期:1998-05-01 00:00:00
abstract::The RCAS retroviral vector was used to express chicken and mouse cellular Jun proteins in chicken embryo fibroblasts. Both mouse and chicken proteins induced foci of transformed cells with low to moderate efficiency compared with viral Jun, but were as effective as the viral protein in promoting anchorage-independent ...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1992-10-01 00:00:00
abstract::The c-Myb transcriptional regulator is crucial to the development and functioning of haemopoietic cells, so much so that mouse embryos homozygous for an inactivated c-myb allele die from anaemia at about day 15 of gestation. By analysing c-myb(-/-) chimaeras we show that no mature cells of any lymphoid or myeloid line...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203660
更新日期:2000-07-13 00:00:00
abstract::Clinical and epidemiological data support a role for human papilloma virus (HPV) type 16 in the pathogenesis of cervical carcinoma. The W12 cell line contains HPV16 sequences, predominantly as a high copy number episome, and is immortalised in vitro, but non-tumourigenic. A morphologically distinct sub-line of the par...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1990-04-01 00:00:00