Bioluminescence imaging captures the expression and dynamics of endogenous p21 promoter activity in living mice and intact cells.

Abstract:

:To interrogate endogenous p21(WAF1/CIP1) (p21) promoter activity under basal conditions and in response to various forms of stress, knock-in imaging reporter mice in which expression of firefly luciferase (FLuc) was placed under the control of the endogenous p21 promoter within the Cdkn1a gene locus were generated. Bioluminescence imaging (BLI) of p21 promoter activity was performed noninvasively and repetitively in mice and in cells derived from these mice. We demonstrated that expression of FLuc accurately reported endogenous p21 expression at baseline and under conditions of genotoxic stress and that photon flux correlated with mRNA abundance and, therefore, bioluminescence provided a direct readout of p21 promoter activity in vivo. BLI confirmed that p53 was required for activation of the p21 promoter in vivo in response to ionizing radiation. Interestingly, imaging of reporter cells demonstrated that p53 prevents the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway from activating p21 expression when quiescent cells are stimulated with serum to reenter the cell cycle. In addition, low-light BLI identified p21 expression in specific regions of individual organs that had not been observed previously. This inducible p21(FLuc) knock-in reporter strain will facilitate imaging studies of p53-dependent and -independent stress responses within the physiological context of the whole animal.

journal_name

Mol Cell Biol

authors

Tinkum KL,Marpegan L,White LS,Sun J,Herzog ED,Piwnica-Worms D,Piwnica-Worms H

doi

10.1128/MCB.05243-11

subject

Has Abstract

pub_date

2011-09-01 00:00:00

pages

3759-72

issue

18

eissn

0270-7306

issn

1098-5549

pii

MCB.05243-11

journal_volume

31

pub_type

杂志文章
  • Meiotic recombination between repeated transposable elements in Saccharomyces cerevisiae.

    abstract::We have measured the frequency of meiotic recombination between marked Ty elements in the Saccharomyces cerevisiae genome. These recombination events were usually nonreciprocal (gene conversions) and sometimes involved nonhomologous chromosomes. The frequency of ectopic gene conversion among Ty elements appeared lower...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.7.2942

    authors: Kupiec M,Petes TD

    更新日期:1988-07-01 00:00:00

  • Neutral sphingomyelinase 1 deficiency in the mouse causes no lipid storage disease.

    abstract::Sphingomyelin is a major lipid in the bilayer of subcellular membranes of eukaryotic cells. Different sphingomyelinases catalyze the initial step in the catabolism of sphingomyelin, the hydrolysis to phosphocholine and ceramide. Sphingomyelinases have been postulated to generate ceramide as a lipophilic second messeng...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.11.3633-3638.2002

    authors: Zumbansen M,Stoffel W

    更新日期:2002-06-01 00:00:00

  • Characterization of the inducer of short transcripts, a human immunodeficiency virus type 1 transcriptional element that activates the synthesis of short RNAs.

    abstract::The inducer of short transcripts, or IST, is an unusual transcriptional element located downstream of the human immunodeficiency virus type 1 (HIV-1) promoter. IST activates HIV-1 transcription, but the resulting RNAs are short and end at approximately position +59. IST, therefore, appears to promote the formation of ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.2.1251

    authors: Sheldon M,Ratnasabapathy R,Hernandez N

    更新日期:1993-02-01 00:00:00

  • Polyamines regulate the stability of JunD mRNA by modulating the competitive binding of its 3' untranslated region to HuR and AUF1.

    abstract::Polyamines critically regulate all mammalian cell growth and proliferation by mechanisms such as the repression of growth-inhibitory proteins, including JunD. Decreasing the levels of cellular polyamines stabilizes JunD mRNA without affecting its transcription, but the exact mechanism whereby polyamines regulate JunD ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00807-10

    authors: Zou T,Rao JN,Liu L,Xiao L,Yu TX,Jiang P,Gorospe M,Wang JY

    更新日期:2010-11-01 00:00:00

  • Delayed wound healing in keratin 6a knockout mice.

    abstract::Keratin 6 (K6) expression in the epidermis has two components: constitutive expression in the innermost layer of the outer root sheath (ORS) of hair follicles and inducible expression in the interfollicular epidermis in response to stressful stimuli such as wounding. Mice express two K6 isoforms, MK6a and MK6b. To gai...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.14.5248-5255.2000

    authors: Wojcik SM,Bundman DS,Roop DR

    更新日期:2000-07-01 00:00:00

  • Activated polo-like kinase Plx1 is required at multiple points during mitosis in Xenopus laevis.

    abstract::Entry into mitosis depends upon activation of the dual-specificity phosphatase Cdc25C, which dephosphorylates and activates the cyclin B-Cdc2 complex. Previous work has shown that the Xenopus polo-like kinase Plx1 can phosphorylate and activate Cdc25C in vitro. In the work presented here, we demonstrate that Plx1 is a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.7.4262

    authors: Qian YW,Erikson E,Li C,Maller JL

    更新日期:1998-07-01 00:00:00

  • Zebra fish myc family and max genes: differential expression and oncogenic activity throughout vertebrate evolution.

    abstract::To gain insight into the role of Myc family oncoproteins and their associated protein Max in vertebrate growth and development, we sought to identify homologs in the zebra fish (Brachydanio rerio). A combination of a polymerase chain reaction-based cloning strategy and low-stringency hybridization screening allowed fo...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.5.2765

    authors: Schreiber-Agus N,Horner J,Torres R,Chiu FC,DePinho RA

    更新日期:1993-05-01 00:00:00

  • Molecular mechanism for a role of SHP2 in epidermal growth factor receptor signaling.

    abstract::The Src homology 2-containing phosphotyrosine phosphatase (SHP2) is primarily a positive effector of receptor tyrosine kinase signaling. However, the molecular mechanism by which SHP2 effects its biological function is unknown. In this report, we provide evidence that defines the molecular mechanism and site of action...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.21.7875-7886.2003

    authors: Agazie YM,Hayman MJ

    更新日期:2003-11-01 00:00:00

  • Inhibition of E2F activity by the cyclin-dependent protein kinase inhibitor p21 in cells expressing or lacking a functional retinoblastoma protein.

    abstract::p21Sdi1/WAF1/Cip1 inhibits cyclin-dependent protein kinases and cell proliferation. p21 is presumed to inhibit growth by preventing the phosphorylation of growth-regulatory proteins, including the retinoblastoma tumor suppressor protein (pRb). The ultimate effector(s) of p21 growth inhibition, however, is largely a ma...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.6.2987

    authors: Dimri GP,Nakanishi M,Desprez PY,Smith JR,Campisi J

    更新日期:1996-06-01 00:00:00

  • Involvement of retinoblastoma protein and HBP1 in histone H1(0) gene expression.

    abstract::The histone H1(0)-encoding gene is expressed in vertebrates in differentiating cells during the arrest of proliferation. In the H1(0) promoter, a specific regulatory element, which we named the H4 box, exhibits features which implicate a role in mediating H1(0) gene expression in response to both differentiation and c...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.18.6627-6637.2000

    authors: Lemercier C,Duncliffe K,Boibessot I,Zhang H,Verdel A,Angelov D,Khochbin S

    更新日期:2000-09-01 00:00:00

  • Post-translational regulation of the 54K cellular tumor antigen in normal and transformed cells.

    abstract::The 54K cellular tumor antigen has been translated in vitro, using messenger ribonucleic acids from simian virus 40 (SV40)-transformed cells or 3T3 cells. The in vitro 54K product could be immunoprecipitated with SV40 tumor serum and had a peptide map that was similar, but not identical, to the in vivo product. The le...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.1.2.101

    authors: Oren M,Maltzman W,Levine AJ

    更新日期:1981-02-01 00:00:00

  • DNA sequence, structure, and tyrosine kinase activity of the Drosophila melanogaster Abelson proto-oncogene homolog.

    abstract::We report our molecular characterization of the Drosophila melanogaster Abelson gene (abl), a gene in which recessive loss-of-function mutations result in lethality at the pupal stage of development. This essential gene consists of 10 exons extending over 26 kilobase pairs of genomic DNA. The DNA sequence encodes a pr...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.2.843

    authors: Henkemeyer MJ,Bennett RL,Gertler FB,Hoffmann FM

    更新日期:1988-02-01 00:00:00

  • Tyrosine phosphorylation sites at amino acids 239 and 240 of Shc are involved in epidermal growth factor-induced mitogenic signaling that is distinct from Ras/mitogen-activated protein kinase activation.

    abstract::Epidermal growth factor (EGF) induces tyrosine phosphorylation of the Shc adapter protein, which plays an important role in EGF-stimulated mitogenesis. Shc stimulates Ras/mitogen-activated protein kinase (MAPK) through forming a complex with Grb2 at the phosphorylated tyrosine (Y) residue 317. In this study, we identi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.4.1824

    authors: Gotoh N,Toyoda M,Shibuya M

    更新日期:1997-04-01 00:00:00

  • Functional requirement for histone deacetylase 1 in Caenorhabditis elegans gonadogenesis.

    abstract::Histone acetylation and deacetylation have been implicated in the regulation of gene expression. Molecular studies have shown that histone deacetylases (HDACs) function as transcriptional repressors. However, very little is known about their roles during development in multicellular organisms. We previously demonstrat...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.9.3024-3034.2002

    authors: Dufourcq P,Victor M,Gay F,Calvo D,Hodgkin J,Shi Y

    更新日期:2002-05-01 00:00:00

  • The Int-2/Fgf-3 oncogene product is secreted and associates with extracellular matrix: implications for cell transformation.

    abstract::NIH3T3 cells transformed by mouse Int-2/Fgf-3 cDNA express a series of Int-2-related products representing discrete stages of processing and glycosylation. We confirm that in at least two highly transformed clonal lines, Int-2 products acquire further modifications and are efficiently secreted into the culture medium....

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.12.5929

    authors: Kiefer P,Peters G,Dickson C

    更新日期:1991-12-01 00:00:00

  • Characterization of a telomere-binding protein from Physarum polycephalum.

    abstract::We have partially purified a nuclear protein (PPT) from Physarum polycephalum that binds to the extrachromosomal ribosomal DNA telomeres of this acellular slime mold. Binding is specific for the (T2AG3)n telomere repeats, as evidenced by nitrocellulose filter binding assays, by gel mobility shift assays with both DNA ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.4.2282

    authors: Coren JS,Epstein EM,Vogt VM

    更新日期:1991-04-01 00:00:00

  • Expression of interferon consensus sequence binding protein (ICSBP) is downregulated in Bcr-Abl-induced murine chronic myelogenous leukemia-like disease, and forced coexpression of ICSBP inhibits Bcr-Abl-induced myeloproliferative disorder.

    abstract::Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder resulting from the neoplastic transformation of a hematopoietic stem cell. The majority of cases of CML are associated with the (9;22) chromosome translocation that generates the bcr-abl chimeric gene. Alpha interferon (IFN-alpha) treatment ind...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.4.1149-1161.2000

    authors: Hao SX,Ren R

    更新日期:2000-02-01 00:00:00

  • Potentiation of protein kinase C zeta activity by 15-deoxy-delta(12,14)-prostaglandin J(2) induces an imbalance between mitogen-activated protein kinases and NF-kappa B that promotes apoptosis in macrophages.

    abstract::Activation of the macrophage cell line RAW 264.7 with lipopolysaccharide (LPS) transiently activates protein kinase C zeta (PKC zeta) and Jun N-terminal kinase (JNK) through a phosphoinositide-3-kinase (PI3-kinase)-dependent pathway. Incubation of LPS-treated cells with the cyclopentenone 15-deoxy-Delta(12,14)-prostag...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.4.1196-1208.2003

    authors: Castrillo A,Través PG,Martín-Sanz P,Parkinson S,Parker PJ,Boscá L

    更新日期:2003-02-01 00:00:00

  • Two upstream activation sequences control the expression of the XPR2 gene in the yeast Yarrowia lipolytica.

    abstract::We have initiated a study of the promoter region of the alkaline extracellular protease gene (XPR2) from Yarrowia lipolytica to identify upstream sequences possibly involved in carbon, nitrogen, and peptone control of XPR2 expression. Deletion analysis showed that the TATA box and two major upstream activation sequenc...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.1.327

    authors: Blanchin-Roland S,Cordero Otero RR,Gaillardin C

    更新日期:1994-01-01 00:00:00

  • The human SPT20-containing SAGA complex plays a direct role in the regulation of endoplasmic reticulum stress-induced genes.

    abstract::One of the central questions in eukaryotic transcription is how activators can transmit their signal to stimulate gene expression in the context of chromatin. The multisubunit SAGA coactivator complex has both histone acetyltransferase and deubiquitination activities and remodels chromatin to allow transcription. Whet...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01076-08

    authors: Nagy Z,Riss A,Romier C,le Guezennec X,Dongre AR,Orpinell M,Han J,Stunnenberg H,Tora L

    更新日期:2009-03-01 00:00:00

  • A role for SMN exon 7 splicing in the selective vulnerability of motor neurons in spinal muscular atrophy.

    abstract::Spinal muscular atrophy (SMA) is an inherited motor neuron disease caused by homozygous loss of the Survival Motor Neuron 1 (SMN1) gene. In the absence of SMN1, inefficient inclusion of exon 7 in transcripts from the nearly identical SMN2 gene results in ubiquitous SMN decrease but selective motor neuron degeneration....

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.06077-11

    authors: Ruggiu M,McGovern VL,Lotti F,Saieva L,Li DK,Kariya S,Monani UR,Burghes AH,Pellizzoni L

    更新日期:2012-01-01 00:00:00

  • Maintenance of protein synthesis in spite of mRNA breakdown in interferon-treated HeLa cells infected with reovirus.

    abstract::Interferon induces the synthesis of an enzyme which synthesizes 2',5'-oligoadenylate [2',5'-oligo(A)] when activated by double-stranded RNA. The 2',5'-oligo(A) in turn activates an endonuclease (RNase L). Concentrations of 2',5'-oligo(A) sufficient to activate RNase L are formed in interferon-treated HeLa cells infect...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.3.1.64

    authors: Nilsen TW,Maroney PA,Baglioni C

    更新日期:1983-01-01 00:00:00

  • Placental failure in mice lacking the mammalian homolog of glial cells missing, GCMa.

    abstract::The GCM family of transcription factors consists of Drosophila melanogaster GCM, an important regulator of gliogenesis in the fly, and its two mammalian homologs, GCMa and GCMb. To clarify the function of these mammalian homologs, we deleted GCMa in mice. Genetic ablation of murine GCMa (mGCMa) is embryonic lethal, wi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.7.2466-2474.2000

    authors: Schreiber J,Riethmacher-Sonnenberg E,Riethmacher D,Tuerk EE,Enderich J,Bösl MR,Wegner M

    更新日期:2000-04-01 00:00:00

  • The RPC31 gene of Saccharomyces cerevisiae encodes a subunit of RNA polymerase C (III) with an acidic tail.

    abstract::The RPC31 gene encoding the C31 subunit of Saccharomyces cerevisiae RNA polymerase C (III) has been isolated, starting from a C-terminal fragment cloned on a lambda gt11 library. It is unique on the yeast genome and lies on the left arm of chromosome XIV, very close to a NotI site. Its coding sequence perfectly matche...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.9.4737

    authors: Mosrin C,Riva M,Beltrame M,Cassar E,Sentenac A,Thuriaux P

    更新日期:1990-09-01 00:00:00

  • Cooperative interaction between hepatocyte nuclear factor 4 alpha and GATA transcription factors regulates ATP-binding cassette sterol transporters ABCG5 and ABCG8.

    abstract::Cholesterol homeostasis is maintained by coordinate regulation of cholesterol synthesis and its conversion to bile acids in the liver. The excretion of cholesterol from liver and intestine is regulated by ATP-binding cassette half-transporters ABCG5 and ABCG8. The genes for these two proteins are closely linked and di...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01894-06

    authors: Sumi K,Tanaka T,Uchida A,Magoori K,Urashima Y,Ohashi R,Ohguchi H,Okamura M,Kudo H,Daigo K,Maejima T,Kojima N,Sakakibara I,Jiang S,Hasegawa G,Kim I,Osborne TF,Naito M,Gonzalez FJ,Hamakubo T,Kodama T,Sakai J

    更新日期:2007-06-01 00:00:00

  • The loss of RGS protein-Gα(i2) interactions results in markedly impaired mouse neutrophil trafficking to inflammatory sites.

    abstract::Neutrophils are first responders rapidly mobilized to inflammatory sites by a tightly regulated, nonredundant hierarchy of chemoattractants. These chemoattractants engage neutrophil cell surface receptors triggering heterotrimeric G-protein Gα(i) subunits to exchange GDP for GTP. By limiting the duration that Gα(i) su...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00651-12

    authors: Cho H,Kamenyeva O,Yung S,Gao JL,Hwang IY,Park C,Murphy PM,Neubig RR,Kehrl JH

    更新日期:2012-11-01 00:00:00

  • SUN1 interacts with nuclear lamin A and cytoplasmic nesprins to provide a physical connection between the nuclear lamina and the cytoskeleton.

    abstract::Nuclear migration and positioning within cells are critical for many developmental processes and are governed by the cytoskeletal network. Although mechanisms of nuclear-cytoskeletal attachment are unclear, growing evidence links a novel family of nuclear envelope (NE) proteins that share a conserved C-terminal SUN (S...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.26.10.3738-3751.2006

    authors: Haque F,Lloyd DJ,Smallwood DT,Dent CL,Shanahan CM,Fry AM,Trembath RC,Shackleton S

    更新日期:2006-05-01 00:00:00

  • Dominant positive and negative selection using a hygromycin phosphotransferase-thymidine kinase fusion gene.

    abstract::The hygromycin phosphotransferase gene was fused in-frame with the herpes simplex virus type 1 thymidine kinase gene. The resulting fusion gene (termed HyTK) confers hygromycin B resistance for dominant positive selection and ganciclovir sensitivity for negative selection and provides a means by which these selectable...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.11.6.3374

    authors: Lupton SD,Brunton LL,Kalberg VA,Overell RW

    更新日期:1991-06-01 00:00:00

  • A novel intron element operates posttranscriptionally To regulate human N-myc expression.

    abstract::Precisely regulated expression of oncogenes and tumor suppressor genes is essential for normal development, and deregulated expression can lead to cancer. The human N-myc gene normally is expressed in only a subset of fetal epithelial tissues, and its expression is extinguished in all adult tissues except transiently ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.19.1.155

    authors: Sivak LE,Pont-Kingdon G,Le K,Mayr G,Tai KF,Stevens BT,Carroll WL

    更新日期:1999-01-01 00:00:00

  • A functional screen for Myc-responsive genes reveals serine hydroxymethyltransferase, a major source of the one-carbon unit for cell metabolism.

    abstract::A cDNA library enriched with Myc-responsive cDNAs but depleted of myc cDNAs was used in a functional screen for growth enhancement in c-myc-null cells. A cDNA clone for mitochondrial serine hydroxymethyltransferase (mSHMT) that was capable of partial complementation of the growth defects of c-myc-null cells was identi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.22.16.5793-5800.2002

    authors: Nikiforov MA,Chandriani S,O'Connell B,Petrenko O,Kotenko I,Beavis A,Sedivy JM,Cole MD

    更新日期:2002-08-01 00:00:00