A novel p53 mutational hotspot in skin tumors from UV-irradiated Xpc mutant mice alters transactivation functions.

Abstract:

:A mutation in codon 122 of the mouse p53 gene resulting in a T to L amino acid substitution (T122-->L) is frequently associated with skin cancer in UV-irradiated mice that are both homozygous mutant for the nucleotide excision repair (NER) gene Xpc (Xpc(-/-)) and hemizygous mutant for the p53 gene. We investigated the functional consequences of the mouse T122-->L mutation when expressed either in mammalian cells or in the yeast Saccharomyces cerevisiae. Similar to a non-functional allele, high expression of the T122-->L allele in p53(-/-) mouse embryo fibroblasts and human Saos-2 cells failed to suppress growth. However, the T122-->L mutant p53 showed wild-type transactivation levels with Bax and MDM2 promoters when expressed in either cell type and retained transactivation of the p21 and the c-Fos promoters in one cell line. Using a recently developed rheostatable p53 induction system in yeast we assessed the T122-->L transactivation capacity at low levels of protein expression using 12 different p53 response elements (REs). Compared to wild-type p53 the T122-->L protein manifested an unusual transactivation pattern comprising reduced and enhanced activity with specific REs. The high incidence of the T122-->L mutant allele in the Xpc(-/-) background suggests that both genetic and epigenetic conditions may facilitate the emergence of particular functional p53 mutations. Furthermore, the approach that we have taken also provides for the dissection of functions that may be retained in many p53 tumor alleles.

journal_name

Oncogene

journal_title

Oncogene

authors

Inga A,Nahari D,Velasco-Miguel S,Friedberg EC,Resnick MA

doi

10.1038/sj.onc.1205779

subject

Has Abstract

pub_date

2002-08-22 00:00:00

pages

5704-15

issue

37

eissn

0950-9232

issn

1476-5594

journal_volume

21

pub_type

杂志文章

相关文献

ONCOGENE文献大全
  • Dominant negative Met reduces tumorigenicity-metastasis and increases tubule formation in mammary cells.

    abstract::Activation of the Met tyrosine kinase growth factor receptor by its ligand HGF/SF has been shown to increase in vitro invasiveness in epithelial cell lines. To study the effect of Met-HGF/SF signaling in breast cancer cells, we transfected met, hgf/sf and dominant negative (DN) forms of met into the poorly differentia...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203557

    authors: Firon M,Shaharabany M,Altstock RT,Horev J,Abramovici A,Resau JH,Vande Woude GF,Tsarfaty I

    更新日期:2000-05-11 00:00:00

  • Identification of NF-kappa B-regulated genes induced by TNFalpha utilizing expression profiling and RNA interference.

    abstract::Tumor necrosis factor alpha (TNF alpha) is a proinflammatory cytokine with important roles in regulating inflammatory responses as well as cell cycle proliferation and apoptosis. Although TNFalpha stimulates apoptosis, it also activates the transcription factor NF-kappa B, and studies have shown that inhibition of NF-...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206262

    authors: Zhou A,Scoggin S,Gaynor RB,Williams NS

    更新日期:2003-04-03 00:00:00

  • Tumor suppressor Pdcd4 inhibits invasion/intravasation and regulates urokinase receptor (u-PAR) gene expression via Sp-transcription factors.

    abstract::Tumor suppressor Pdcd4 has recently been shown to inhibit invasion by activating activator protein-1 (AP-1); however, little is known of the functionally significant Pdcd4-target genes. The urokinase receptor (u-PAR) promotes invasion/metastasis, and is associated with poor cancer-patient survival. The present study w...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210234

    authors: Leupold JH,Yang HS,Colburn NH,Asangani I,Post S,Allgayer H

    更新日期:2007-07-05 00:00:00

  • Chk1 deficiency in the mouse small intestine results in p53-independent crypt death and subsequent intestinal compensation.

    abstract::Chk1 is a serine/threonine protein kinase that is activated by a wide range of DNA-damaging agents to slow the cell cycle during S phase and G2/M. Abrogation of these cell-cycle checkpoints using Chk1 inhibitors results in hypersensitivity to DNA-damaging agents in vitro and may provide a potential therapeutic tool to...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2008.482

    authors: Greenow KR,Clarke AR,Jones RH

    更新日期:2009-03-19 00:00:00

  • Cleaved high-molecular-weight kininogen and its domain 5 inhibit migration and invasion of human prostate cancer cells through the epidermal growth factor receptor pathway.

    abstract::Upregulation and activation of epidermal growth factor receptor and/or urokinase-type plasminogen activator receptor in a variety of cancers have been shown to be associated with poor prognosis. High-molecular-weight kininogen can be hydrolysed by plasma kallikrein to bradykinin and cleaved high-molecular-weight kinin...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2009.132

    authors: Liu Y,Pixley R,Fusaro M,Godoy G,Kim E,Bromberg ME,Colman RW

    更新日期:2009-07-30 00:00:00

  • Prognostic value of the hDMP1-ARF-Hdm2-p53 pathway in breast cancer.

    abstract::Our recent study showed critical roles of Dmp1 as a sensor of oncogenic Ras, HER2/neu signaling and activation of the Arf-p53 pathway. To elucidate the role of human DMP1 (hDMP1) in breast cancer, one hundred and ten pairs of human breast cancer specimen were studied for the alterations of the hDMP1-ARF-Hdm2-p53 pathw...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.423

    authors: Maglic D,Zhu S,Fry EA,Taneja P,Kai F,Kendig RD,Sugiyama T,Miller LD,Willingham MC,Inoue K

    更新日期:2013-08-29 00:00:00

  • PKA signaling drives mammary tumorigenesis through Src.

    abstract::Protein kinase A (PKA) hyperactivation causes hereditary endocrine neoplasias; however, its role in sporadic epithelial cancers is unknown. Here, we show that heightened PKA activity in the mammary epithelium generates tumors. Mammary-restricted biallelic ablation of Prkar1a, which encodes for the critical type-I PKA ...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2014.41

    authors: Beristain AG,Molyneux SD,Joshi PA,Pomroy NC,Di Grappa MA,Chang MC,Kirschner LS,Privé GG,Pujana MA,Khokha R

    更新日期:2015-02-26 00:00:00

  • Epigenetic regulations in hematopoietic Hox code.

    abstract::Hox genes encode DNA-binding proteins that are deployed in overlapping domains along various body axes during embryonic development. This sequential activation of Hox genes in temporal and spatial mode, the Hox code, is critical for the proper positioning of segmented structures along those axes, which include the ver...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/onc.2010.484

    authors: He H,Hua X,Yan J

    更新日期:2011-01-27 00:00:00

  • Allelic deletions at chromosome 11q22-q23.1 and 11q25-qterm are frequent in sporadic breast but not colorectal cancers.

    abstract::We identified the chromosome 11q23 region as containing a putative tumour suppressor gene(s) frequently deleted in nonfamilial breast and other cancers. To define this region(s) further, we performed a systematic genetic analysis at chromosome 11q14-qterm in sporadic breast and colorectal cancer. Tumour and constituti...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1200847

    authors: Koreth J,Bakkenist CJ,McGee JO

    更新日期:1997-01-30 00:00:00

  • Elevated Mdm2 expression induces chromosomal instability and confers a survival and growth advantage to B cells.

    abstract::Mdm2, a regulator of the p53 tumor suppressor, is frequently overexpressed in lymphomas, including lymphomas that have inactivated p53. However, the biological consequences of Mdm2 overexpression in lymphocytes are not fully resolved. Here, we report that increased expression of Mdm2 in B cells augmented proliferation...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1210788

    authors: Wang P,Lushnikova T,Odvody J,Greiner TC,Jones SN,Eischen CM

    更新日期:2008-03-06 00:00:00

  • Kinase activity-independent suppression of p73alpha by AMP-activated kinase alpha (AMPKalpha).

    abstract::Although p73alpha induces many of the same cellular events as p53, it is structurally distinct from p53 in that it possesses a unique COOH-terminal domain. To dissect the function of this domain, we performed yeast two-hybrid screening of a HeLa cDNA library using residues 552-636 of p73alpha as bait. Among the clones...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2008.452

    authors: Lee YG,Lee SW,Sin HS,Kim EJ,Um SJ

    更新日期:2009-02-19 00:00:00

  • Expression of constitutively nuclear cyclin D1 in murine lymphocytes induces B-cell lymphoma.

    abstract::Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by overexpression of cyclin D1 due to the t(11;14) chromosomal translocation. While expression of cyclin D1 correlates with MCL development, expression of wild-type (WT) cyclin D1 transgene in murine lymphocytes is unable to drive B-cell lymphoma. As cyclin...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1209147

    authors: Gladden AB,Woolery R,Aggarwal P,Wasik MA,Diehl JA

    更新日期:2006-02-16 00:00:00

  • PTEN, but not SHIP and SHIP2, suppresses the PI3K/Akt pathway and induces growth inhibition and apoptosis of myeloma cells.

    abstract::Expression of PTEN tumor suppressor gene has been known to dephosphorylate the phosphatidylinositol 3' kinase (PI3K) products on the 3 prime inositol ring, resulting in reduced Akt activation. Loss of PTEN expression in OPM2 and delta47 human myeloma lines led to high Akt activity toward insulin-like growth factor I (...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205650

    authors: Choi Y,Zhang J,Murga C,Yu H,Koller E,Monia BP,Gutkind JS,Li W

    更新日期:2002-08-08 00:00:00

  • The rapid destabilization of p53 mRNA in immortal chicken embryo fibroblast cells.

    abstract::The steady-state levels of p53 mRNA were dramatically lower in immortal chicken embryo fibroblast (CEF) cell lines compared to primary CEF cells. In the presence of cycloheximide (CHX), the steady-state levels of p53 mRNA markedly increased in immortal CEF cell lines, similar to levels found in primary cells. The de n...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1204664

    authors: Kim H,You S,Foster LK,Farris J,Foster DN

    更新日期:2001-08-23 00:00:00

  • Cytokine control of developmental programs in normal hematopoiesis and leukemia.

    abstract::The establishment of a system for in vitro clonal development of hematopoietic cells made it possible to discover the cytokines that regulate hematopoiesis. These cytokines include colony stimulating factors and others, which interact in a network, and there is a cytokine cascade which couples growth and differentiati...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1205319

    authors: Lotem J,Sachs L

    更新日期:2002-05-13 00:00:00

  • Smac induces cytochrome c release and apoptosis independently from Bax/Bcl-x(L) in a strictly caspase-3-dependent manner in human carcinoma cells.

    abstract::The mitochondrial apoptosis pathway mediates cell death through the release of various pro-apoptotic factors including cytochrome c and Smac, the second mitochondrial activator of caspases, into the cytosol. Smac was shown previously to inhibit IAP proteins and to facilitate initiation of the caspase cascade upon cyto...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1207594

    authors: Hasenjäger A,Gillissen B,Müller A,Normand G,Hemmati PG,Schuler M,Dörken B,Daniel PT

    更新日期:2004-06-03 00:00:00

  • TrkC signaling is activated in adenoid cystic carcinoma and requires NT-3 to stimulate invasive behavior.

    abstract::Treatment options for adenoid cystic carcinoma (ACC) of the salivary gland, a slowly growing tumor with propensity for neuroinvasion and late recurrence, are limited to surgery and radiotherapy. Based on expression analysis performed on clinical specimens of salivary cancers, we identified in ACC expression of the neu...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2012.377

    authors: Ivanov SV,Panaccione A,Brown B,Guo Y,Moskaluk CA,Wick MJ,Brown JL,Ivanova AV,Issaeva N,El-Naggar AK,Yarbrough WG

    更新日期:2013-08-08 00:00:00

  • HPV16 E6 and E7 upregulate the histone lysine demethylase KDM2B through the c-MYC/miR-146a-5p axys.

    abstract::Persistent infection by high-risk human papillomaviruses (HPVs) is associated with the development of cervical cancer and a subset of anogenital and head and neck squamous cell carcinomas. Abnormal expression of cellular microRNAs (miRNAs) plays an important role in the development of cancer, including HPV-related tum...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/s41388-017-0083-1

    authors: Peta E,Sinigaglia A,Masi G,Di Camillo B,Grassi A,Trevisan M,Messa L,Loregian A,Manfrin E,Brunelli M,Martignoni G,Palù G,Barzon L

    更新日期:2018-03-01 00:00:00

  • Regulation of autophagy by ATF4 in response to severe hypoxia.

    abstract::Activating transcription factor 4 (ATF4) is a transcription factor induced under severe hypoxia and a component of the PERK pathway involved in the unfolded protein response (UPR), a process that protects cells from the negative consequences of endoplasmic reticulum (ER) stress. In this study, we have used small inter...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2010.191

    authors: Rzymski T,Milani M,Pike L,Buffa F,Mellor HR,Winchester L,Pires I,Hammond E,Ragoussis I,Harris AL

    更新日期:2010-08-05 00:00:00

  • Ero1-L alpha plays a key role in a HIF-1-mediated pathway to improve disulfide bond formation and VEGF secretion under hypoxia: implication for cancer.

    abstract::Oxygen is the ultimate source of oxidizing power for disulfide bond formation, suggesting that under limiting oxygen proper protein folding might be compromised. We show that secretion of vascular endothelial growth factor (VEGF), a protein with multiple disulfide bonds, was indeed impeded under hypoxia and was partia...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1208325

    authors: May D,Itin A,Gal O,Kalinski H,Feinstein E,Keshet E

    更新日期:2005-02-03 00:00:00

  • Cdx1 inhibits the proliferation of human colon cancer cells by reducing cyclin D1 gene expression.

    abstract::The transcription factor Cdx1 regulates intestine-specific gene expression and enterocyte differentiation. It has been hypothesized to play a role in regulating intestinal cell proliferation; however, the mechanism for this effect remains elusive. In a prior study, we demonstrated that Cdx1 expression reduced the prol...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206770

    authors: Lynch J,Keller M,Guo RJ,Yang D,Traber P

    更新日期:2003-09-25 00:00:00

  • Distinct methylation patterns of two APC gene promoters in normal and cancerous gastric epithelia.

    abstract::The adenomatous polyposis coli (APC) tumor suppressor gene is mutationally inactivated in both familial and sporadic forms of colorectal cancers. In addition, hypermethylation of CpG islands in the upstream portion of APC, a potential alternative mechanism of tumor suppressor gene inactivation, has been described in c...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1203704

    authors: Tsuchiya T,Tamura G,Sato K,Endoh Y,Sakata K,Jin Z,Motoyama T,Usuba O,Kimura W,Nishizuka S,Wilson KT,James SP,Yin J,Fleisher AS,Zou T,Silverberg SG,Kong D,Meltzer SJ

    更新日期:2000-07-27 00:00:00

  • Somatic VHL gene deletion and point mutation in MEN 2A-associated pheochromocytoma.

    abstract::Multiple endocrine neoplasia type 2 (MEN 2) is an inherited cancer syndrome that includes pheochromocytoma. Germline mutations in RET are responsible for MEN 2 but the precise pathogenetic mechanisms of tumorigenesis are unknown. We have recently identified possible mechanisms of tumor formation in patients with MEN 2...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1205133

    authors: Koch CA,Huang SC,Zhuang Z,Stolle C,Azumi N,Chrousos GP,Vortmeyer AO,Pacak K

    更新日期:2002-01-17 00:00:00

  • Therapeutic approaches to AIDS-related malignancies.

    abstract::The introduction of highly active antiretroviral therapy (HAART) has changed dramatically the landscape of HIV disease. Deaths from AIDS-related diseases have been reduced by 75% since protease inhibitor therapy and combination antiretroviral therapy came into use in late 1995. While KS is declining, the situation for...

    journal_title:Oncogene

    pub_type: 杂志文章,评审

    doi:10.1038/sj.onc.1206771

    authors: Berretta M,Cinelli R,Martellotta F,Spina M,Vaccher E,Tirelli U

    更新日期:2003-09-29 00:00:00

  • Involvement of poly (ADP-ribose)-polymerase in the Pax-6 gene regulation in neuroretina.

    abstract::The quail Pax-6 gene is expressed from two promoters named P0 and P1. P0 promoter is under the control of a neuroretina-specific enhancer (EP). This enhancer activates the P0 promoter specifically in neuroretina cells and in a developmental stage-dependent manner. The EP enhancer binds efficiently, as revealed by sout...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1202406

    authors: Plaza S,Aumercier M,Bailly M,Dozier C,Saule S

    更新日期:1999-01-28 00:00:00

  • Cisplatin treatment increases survival and expansion of a highly tumorigenic side-population fraction by upregulating VEGF/Flt1 autocrine signaling.

    abstract::The cellular and molecular mechanisms of tumor progression following chemotherapy are largely unknown. Here, we demonstrate that cisplatin (CDDP) treatment upregulates VEGF and Flt1 expression leading to the survival and expansion of a highly tumorigenic fraction of side-population (SP) cells in osteosarcoma (HOS), ne...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2008.38

    authors: Tsuchida R,Das B,Yeger H,Koren G,Shibuya M,Thorner PS,Baruchel S,Malkin D

    更新日期:2008-06-26 00:00:00

  • ALK inhibitor resistance in ALK(F1174L)-driven neuroblastoma is associated with AXL activation and induction of EMT.

    abstract::The crizotinib-resistant ALK(F1174L) mutation arises de novo in neuroblastoma (NB) and is acquired in ALK translocation-driven cancers, lending impetus to the development of novel anaplastic lymphoma kinase (ALK) inhibitors with different modes of action. The diaminopyrimidine TAE684 and its derivative ceritinib (LDK3...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2015.434

    authors: Debruyne DN,Bhatnagar N,Sharma B,Luther W,Moore NF,Cheung NK,Gray NS,George RE

    更新日期:2016-07-14 00:00:00

  • Pleiotropic regulation of macrophage polarization and tumorigenesis by formyl peptide receptor-2.

    abstract::Cancer cells recruit monocytes, macrophages and other inflammatory cells by producing abundant chemoattractants and growth factors, such as macrophage colony-stimulating factor (M-CSF/CSF-1) and monocyte chemoattractant protein-1 (MCP-1/CCL2), to promote tumor growth and dissemination. An understanding of the mechanis...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2011.112

    authors: Li Y,Cai L,Wang H,Wu P,Gu W,Chen Y,Hao H,Tang K,Yi P,Liu M,Miao S,Ye D

    更新日期:2011-09-08 00:00:00

  • Aberrant sensing of extracellular Ca2+ by cultured ataxia telangiectasia fibroblasts.

    abstract::Ataxia telangiectasia (AT) is a human hereditary syndrome whose underlying gene product, ataxia telangiectasia mutated (ATM) protein kinase, is involved in multiple intracellular signaling pathways. We demonstrated previously that AT fibroblasts are defective in intracellular Ca(2+) mobilization in response to both st...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/sj.onc.1206167

    authors: Famulski KS,Al-Hijailan RS,Dobler K,Pienkowska M,Al-Mohanna F,Paterson MC

    更新日期:2003-01-23 00:00:00

  • FOXP3 can modulate TAL1 transcriptional activity through interaction with LMO2.

    abstract::T-cell acute lymphoblastic leukemia (T-ALL) frequently involves aberrant expression of TAL1 (T-cell acute lymphocytic leukemia 1) and LMO2, oncogenic members of the TAL1 transcriptional complex. Transcriptional activity of the TAL1-complex is thought to have a pivotal role in the transformation of thymocytes and is as...

    journal_title:Oncogene

    pub_type: 杂志文章

    doi:10.1038/onc.2015.481

    authors: Fleskens V,Mokry M,van der Leun AM,Huppelschoten S,Pals CE,Peeters J,Coenen S,Cardoso BA,Barata JT,van Loosdregt J,Coffer PJ

    更新日期:2016-08-04 00:00:00