Activation of protein kinase C triggers its ubiquitination and degradation.

Abstract:

:Treatment of cells with tumor-promoting phorbol esters results in the activation but then depletion of phorbol ester-responsive protein kinase C (PKC) isoforms. The ubiquitin-proteasome pathway has been implicated in regulating the levels of many cellular proteins, including those involved in cell cycle control. We report here that in 3Y1 rat fibroblasts, proteasome inhibitors prevent the depletion of PKC isoforms alpha, delta, and epsilon in response to the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Proteasome inhibitors also blocked the tumor-promoting effects of TPA on 3Y1 cells overexpressing c-Src, which results from the depletion of PKC delta. Consistent with the involvement of the ubiquitin-proteasome pathway in the degradation of PKC isoforms, ubiquitinated PKC alpha, delta, and epsilon were detected within 30 min of TPA treatment. Diacylglycerol, the physiological activator of PKC, also stimulated ubiquitination and degradation of PKC, suggesting that ubiquitination is a physiological response to PKC activation. Compounds that inhibit activation of PKC prevented both TPA- and diacylglycerol-induced PKC depletion and ubiquitination. Moreover, a kinase-dead ATP-binding mutant of PKC alpha could not be depleted by TPA treatment. These data are consistent with a suicide model whereby activation of PKC triggers its own degradation via the ubiquitin-proteasome pathway.

journal_name

Mol Cell Biol

authors

Lu Z,Liu D,Hornia A,Devonish W,Pagano M,Foster DA

doi

10.1128/mcb.18.2.839

subject

Has Abstract

pub_date

1998-02-01 00:00:00

pages

839-45

issue

2

eissn

0270-7306

issn

1098-5549

journal_volume

18

pub_type

杂志文章
  • Fragments of ATM which have dominant-negative or complementing activity.

    abstract::The ATM protein has been implicated in pathways controlling cell cycle checkpoints, radiosensitivity, genetic instability, and aging. Expression of ATM fragments containing a leucine zipper motif in a human tumor cell line abrogated the S-phase checkpoint after ionizing irradiation and enhanced radiosensitivity and ch...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.4.2020

    authors: Morgan SE,Lovly C,Pandita TK,Shiloh Y,Kastan MB

    更新日期:1997-04-01 00:00:00

  • Dynamic localization and function of Bni1p at the sites of directed growth in Saccharomyces cerevisiae.

    abstract::Formin homology (FH) proteins are implicated in cell polarization and cytokinesis through actin organization. There are two FH proteins in the yeast Saccharomyces cerevisiae, Bni1p and Bnr1p. Bni1p physically interacts with Rho family small G proteins (Rho1p and Cdc42p), actin, two actin-binding proteins (profilin and...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.21.3.827-839.2001

    authors: Ozaki-Kuroda K,Yamamoto Y,Nohara H,Kinoshita M,Fujiwara T,Irie K,Takai Y

    更新日期:2001-02-01 00:00:00

  • Functional interaction between p53, the TATA-binding protein (TBP), andTBP-associated factors in vivo.

    abstract::The transcriptional activator p53 is known to interact with components of the general transcription factor TFIID in vitro. To examine the relevance of these associations to transcriptional activation in vivo, plasmids expressing a p53-GAL4 chimera and Drosophila TATA-binding protein (dTBP) were transfected into Drosop...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.8.4295

    authors: Farmer G,Colgan J,Nakatani Y,Manley JL,Prives C

    更新日期:1996-08-01 00:00:00

  • Identification of a cysteine-rich receptor for fibroblast growth factors.

    abstract::The fibroblast growth factor (FGF) family consists of seven members whose activities are thought to be mediated by multiple receptors. Here we describe the cDNA cloning, expression, and characterization of a cysteine-rich FGF receptor (CFR) that is distinct from previously identified FGF receptors. The deduced amino a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.12.5600

    authors: Burrus LW,Zuber ME,Lueddecke BA,Olwin BB

    更新日期:1992-12-01 00:00:00

  • Cell-specific interaction of retinoic acid receptors with target genes in mouse embryonic fibroblasts and embryonic stem cells.

    abstract::All-trans retinoic acid (RA) induces transforming growth factor beta (TGF-beta)-dependent autocrine growth of mouse embryonic fibroblasts (MEFs). We have used chromatin immunoprecipitation to map 354 RA receptor (RAR) binding loci in MEFs, most of which were similarly occupied by the RAR alpha and RAR gamma receptors....

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00756-09

    authors: Delacroix L,Moutier E,Altobelli G,Legras S,Poch O,Choukrallah MA,Bertin I,Jost B,Davidson I

    更新日期:2010-01-01 00:00:00

  • Decreased growth of Vhl-/- fibrosarcomas is associated with elevated levels of cyclin kinase inhibitors p21 and p27.

    abstract::Inactivating mutations within the von Hippel-Lindau (VHL) tumor suppressor gene predispose patients to develop a variety of highly vascularized tumors. pVHL targets alpha subunits of the heterodimeric transcription factor hypoxia-inducible factor (HIF), a critical regulator of energy metabolism, angiogenesis, hematopo...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.25.11.4565-4578.2005

    authors: Mack FA,Patel JH,Biju MP,Haase VH,Simon MC

    更新日期:2005-06-01 00:00:00

  • Bcl2's flexible loop domain regulates p53 binding and survival.

    abstract::p53 not only functions as a transcription factor but also has a direct, apoptogenic role at the mitochondria. We have discovered that DNA damage-induced p53-Bcl2 binding is associated with decreased Bcl2-Bax interaction and increased apoptotic cell death in a mechanism regulated by Bcl2's flexible loop regulatory doma...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01647-05

    authors: Deng X,Gao F,Flagg T,Anderson J,May WS

    更新日期:2006-06-01 00:00:00

  • Commitment and effector phases of the physiological cell death pathway elucidated with respect to Bcl-2 caspase, and cyclin-dependent kinase activities.

    abstract::Physiological cell deaths occur ubiquitously throughout biology and have common attributes, including apoptotic morphology with mitosis-like chromatin condensation and prelytic genome digestion. The fundamental question is whether a common mechanism of dying underlies these common hallmarks of death. Here we describe ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.18.5.2912

    authors: Harvey KJ,Blomquist JF,Ucker DS

    更新日期:1998-05-01 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

  • An octamer motif contributes to the expression of the retinoic acid-regulated zinc finger gene Rex-1 (Zfp-42) in F9 teratocarcinoma cells.

    abstract::The message for the zinc finger gene Rex-1 (Zfp-42) is expressed in undifferentiated murine F9 teratocarcinoma cells and embryonic stem cells. Expression of Rex-1 is reduced at the transcriptional level when F9 cells are induced by the addition of retinoic acid (RA) to differentiate. We have isolated genomic DNA for t...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.13.5.2919

    authors: Hosler BA,Rogers MB,Kozak CA,Gudas LJ

    更新日期:1993-05-01 00:00:00

  • Transcriptional properties of BmX, a moderately repetitive silkworm gene that is an RNA polymerase III template.

    abstract::We analyzed the transcriptional properties of a repetitive sequence element, BmX, that belongs to a large gene family (approximately 2 x 10(4) copies) in the genome of the Bombyx mori silkworm. We discovered BmX elements because of their ability to direct transcription by polymerase III in vitro and used them to test ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.2.624

    authors: Wilson ET,Condliffe DP,Sprague KU

    更新日期:1988-02-01 00:00:00

  • Regulation of cyclooxygenase 2 mRNA stability by the mitogen-activated protein kinase p38 signaling cascade.

    abstract::A tetracycline-regulated reporter system was used to investigate the regulation of cyclooxygenase 2 (Cox-2) mRNA stability by the mitogen-activated protein kinase (MAPK) p38 signaling cascade. The stable beta-globin mRNA was rendered unstable by insertion of the 2, 500-nucleotide Cox-2 3' untranslated region (3' UTR)....

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.12.4265-4274.2000

    authors: Lasa M,Mahtani KR,Finch A,Brewer G,Saklatvala J,Clark AR

    更新日期:2000-06-01 00:00:00

  • Multiple cis-acting sequence elements are required for efficient splicing of simian virus 40 small-t antigen pre-mRNA.

    abstract::We have determined the effects of a number of mutations in the small-t antigen mRNA intron on the alternative splicing pattern of the simian virus 40 early transcript. Expansion of the distance separating the small-t pre-mRNA lariat branch point and the shared large T-small t 3' splice site from 18 to 29 nucleotides (...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.8.9.3582

    authors: Fu XY,Colgan JD,Manley JL

    更新日期:1988-09-01 00:00:00

  • Transcriptional activation by TFIIB mutants that are severely impaired in interaction with promoter DNA and acidic activation domains.

    abstract::Biochemical experiments indicate that the general transcription factor IIB (TFIIB) can interact directly with acidic activation domains and that activators can stimulate transcription by increasing recruitment of TFIIB to promoters. For promoters at which recruitment of TFIIB to promoters is limiting in vivo, one woul...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.17.12.6794

    authors: Chou S,Struhl K

    更新日期:1997-12-01 00:00:00

  • Cloning and characterization of two novel thyroid hormone receptor beta isoforms.

    abstract::Thyroid hormone (T(3)) activates nuclear receptor transcription factors, encoded by the TRalpha (NR1A1) and TRbeta (NR1A2) genes, to regulate target gene expression. Several TR isoforms exist, and studies of null mice have identified some unique functions for individual TR variants, although considerable redundancy oc...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.20.22.8329-8342.2000

    authors: Williams GR

    更新日期:2000-11-01 00:00:00

  • Akt-directed glucose metabolism can prevent Bax conformation change and promote growth factor-independent survival.

    abstract::The serine/threonine kinase Akt is a component of many receptor signal transduction pathways and can prevent cell death following growth factor withdrawal. Here, we show that Akt inhibition of cell death is not dependent on new protein translation. Instead, Akt inhibition of cell death requires glucose hydrolysis thro...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.20.7315-7328.2003

    authors: Rathmell JC,Fox CJ,Plas DR,Hammerman PS,Cinalli RM,Thompson CB

    更新日期:2003-10-01 00:00:00

  • Pax5 and linker histone H1 coordinate DNA methylation and histone modifications in the 3' regulatory region of the immunoglobulin heavy chain locus.

    abstract::The 3' regulatory region (3' RR) of the murine immunoglobulin heavy chain (IgH) locus contains multiple DNase I-hypersensitive (hs) sites. Proximal sites hs3A, hs1.2, and hs3B are located in an extensive palindromic region and together with hs4 are associated with enhancers involved in the expression and class switch ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00233-08

    authors: Giambra V,Volpi S,Emelyanov AV,Pflugh D,Bothwell AL,Norio P,Fan Y,Ju Z,Skoultchi AI,Hardy RR,Frezza D,Birshtein BK

    更新日期:2008-10-01 00:00:00

  • Yeast killer plasmid mutations affecting toxin secretion and activity and toxin immunity function.

    abstract::M double-stranded RNA (MdsRNA) plasmid mutants were obtained by mutagenesis and screening of a diploid killer culture partially heat cured of the plasmid, so that a high proportion of the cells could be expected to have only on M plasmid. Mutants with neutral (nonkiller [K-], immune [R+]) or suicide (killer [K+], sens...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.2.4.346

    authors: Bussey H,Sacks W,Galley D,Saville D

    更新日期:1982-04-01 00:00:00

  • Topological requirements for homologous recombination among DNA molecules transfected into mammalian cells.

    abstract::Cultured animal cells rearrange foreign DNA very efficiently by homologous recombination. The individual steps that constitute the mechanism(s) of homologous recombination in transfected DNA are as yet undefined. In this study, we examined the topological requirements by using the genome of simian virus 40 (SV40) as a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.5.8.2080

    authors: Wake CT,Vernaleone F,Wilson JH

    更新日期:1985-08-01 00:00:00

  • Alternative excision products originating from a single integration of polyomavirus DNA.

    abstract::The Cyp cell line consists of mouse cells transformed by a thermosensitive polyomavirus (Py) genome and routinely propagated at 39 degrees C. Cyp cells are readily induced to synthesize free Py DNA by being transferred to 33 degrees C. In one subclone (C12/a1/S48, or S48) of this line, such induction resulted in the i...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.5.10.2608

    authors: Huberdeau D,Sylla BS,Herring-Gillam E,Bourgaux-Ramoisy D,Bourgaux P

    更新日期:1985-10-01 00:00:00

  • A mitochondrial retroplasmid integrates into mitochondrial DNA by a novel mechanism involving the synthesis of a hybrid cDNA and homologous recombination.

    abstract::The Mauriceville and Varkud mitochondrial plasmids of Neurospora spp. are closely related, small circular DNAs that propagate via an RNA intermediate and reverse transcription. Although the plasmids ordinarily replicate autonomously, they can also integrate into mitochondrial DNA (mtDNA), yielding defective mtDNAs tha...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.10.6419

    authors: Chiang CC,Kennell JC,Wanner LA,Lambowitz AM

    更新日期:1994-10-01 00:00:00

  • Induction of meiosis in Saccharomyces cerevisiae depends on conversion of the transcriptional represssor Ume6 to a positive regulator by its regulated association with the transcriptional activator Ime1.

    abstract::The transcription of meiosis-specific genes, as well as the initiation of meiosis, in the budding yeast Saccharomyces cerevisiae depends on IME1. IME1 encodes a transcriptional activator which lacks known DNA binding motifs. In this study we have determined the mode by which Ime1 specifically activates the transcripti...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.5.2518

    authors: Rubin-Bejerano I,Mandel S,Robzyk K,Kassir Y

    更新日期:1996-05-01 00:00:00

  • Commitment point during G0-->G1 that controls entry into the cell cycle.

    abstract::Initiation of T-lymphocyte-mediated immune responses involves two cellular processes: entry into the cell cycle (G(0)-->G(1)) for clonal proliferation and coordinated changes in surface and secreted molecules that mediate effector functions. However, a point during G(0)-->G(1) beyond which T cells are committed to ent...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.23.7.2351-2361.2003

    authors: Lea NC,Orr SJ,Stoeber K,Williams GH,Lam EW,Ibrahim MA,Mufti GJ,Thomas NS

    更新日期:2003-04-01 00:00:00

  • Renal Anemia Model Mouse Established by Transgenic Rescue with an Erythropoietin Gene Lacking Kidney-Specific Regulatory Elements.

    abstract::The erythropoietin (Epo) gene is under tissue-specific inducible regulation. Because the kidney is the primary EPO-producing tissue in adults, impaired EPO production in chronic kidney disorders results in serious renal anemia. The Epo gene contains a liver-specific enhancer in the 3' region, but the kidney-specific e...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.00451-16

    authors: Hirano I,Suzuki N,Yamazaki S,Sekine H,Minegishi N,Shimizu R,Yamamoto M

    更新日期:2017-02-01 00:00:00

  • Transforming growth factor beta 1-responsive element: closely associated binding sites for USF and CCAAT-binding transcription factor-nuclear factor I in the type 1 plasminogen activator inhibitor gene.

    abstract::Transforming growth factor beta (TGF-beta) is the name of a group of closely related polypeptides characterized by a multiplicity of effects, including regulation of extracellular proteolysis and turnover of the extracellular matrix. Its cellular mechanism of action is largely unknown. TGF-beta 1 is a strong and fast ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.4.1846

    authors: Riccio A,Pedone PV,Lund LR,Olesen T,Olsen HS,Andreasen PA

    更新日期:1992-04-01 00:00:00

  • Functional cooperation between the proteins Nck and ADAP is fundamental for actin reorganization.

    abstract::T cell antigen receptor (TCR) activation triggers profound changes in the actin cytoskeleton. In addition to controlling cellular shape and polarity, this process regulates vital T cell responses, such as T cell adhesion, motility, and proliferation. These depend on the recruitment of the signaling proteins Nck and Wi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/MCB.01358-10

    authors: Pauker MH,Reicher B,Fried S,Perl O,Barda-Saad M

    更新日期:2011-07-01 00:00:00

  • A novel repressor, par-4, modulates transcription and growth suppression functions of the Wilms' tumor suppressor WT1.

    abstract::The tumor suppressor WT1 represses and activates transcription. The loss and/or imbalance of the dual transcriptional activity of WT1 may contribute to Wilms' tumor. In this study, we identified par-4 (for prostate apoptosis response) as a WT1-interacting protein that itself functions as a transcriptional repressor. p...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.16.12.6945

    authors: Johnstone RW,See RH,Sells SF,Wang J,Muthukkumar S,Englert C,Haber DA,Licht JD,Sugrue SP,Roberts T,Rangnekar VM,Shi Y

    更新日期:1996-12-01 00:00:00

  • Novel DNA-binding proteins regulate intestine-specific transcription of the sucrase-isomaltase gene.

    abstract::Sucrase-isomaltase (SI) is an enterocyte-specific gene which exhibits a complex pattern of expression during intestinal development and in the adult intestinal mucosa. In the studies described in this report, we demonstrate that enterocyte-specific transcription of the SI gene is regulated by an evolutionarily conserv...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.12.8.3614

    authors: Traber PG,Wu GD,Wang W

    更新日期:1992-08-01 00:00:00

  • scid cells efficiently integrate hairpin and linear DNA substrates.

    abstract::The scid mouse mutation affects V(D)J rearrangement and double-strand break repair. scid V(D)J rearrangement is characterized by defective coding joint formation which prevents the development of mature B and T cells. Hairpin DNA has been implicated in the formation of V(D)J coding joints. We found scid cells to be pr...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.14.6.3876

    authors: Staunton JE,Weaver DT

    更新日期:1994-06-01 00:00:00

  • Identification and functional characterization of the human T-cell receptor beta gene transcriptional enhancer: common nuclear proteins interact with the transcriptional regulatory elements of the T-cell receptor alpha and beta genes.

    abstract::A transcriptional enhancer has been mapped to a region 5.5 kilobases 3' of the C beta 2 gene in the human T-cell receptor (TCR) beta-chain locus. Transient transfections allowed localization of enhancer activity to a 480-base-pair HincII-XbaI restriction enzyme fragment. The TCR beta enhancer was active on both the mi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章

    doi:10.1128/mcb.10.10.5486

    authors: Gottschalk LR,Leiden JM

    更新日期:1990-10-01 00:00:00