当前位置： SCI文献检索 > GENES & DEVELOPMENT期刊下所有文献 > Proteomic analysis of pRb loss highlights a signature of decreased mitochondrial oxidative phosphorylation.

Proteomic analysis of pRb loss highlights a signature of decreased mitochondrial oxidative phosphorylation.

Abstract：

:The retinoblastoma tumor suppressor (pRb) protein associates with chromatin and regulates gene expression. Numerous studies have identified Rb-dependent RNA signatures, but the proteomic effects of Rb loss are largely unexplored. We acutely ablated Rb in adult mice and conducted a quantitative analysis of RNA and proteomic changes in the colon and lungs, where Rb(KO) was sufficient or insufficient to induce ectopic proliferation, respectively. As expected, Rb(KO) caused similar increases in classic pRb/E2F-regulated transcripts in both tissues, but, unexpectedly, their protein products increased only in the colon, consistent with its increased proliferative index. Thus, these protein changes induced by Rb loss are coupled with proliferation but uncoupled from transcription. The proteomic changes in common between Rb(KO) tissues showed a striking decrease in proteins with mitochondrial functions. Accordingly, RB1 inactivation in human cells decreased both mitochondrial mass and oxidative phosphorylation (OXPHOS) function. RB(KO) cells showed decreased mitochondrial respiratory capacity and the accumulation of hypopolarized mitochondria. Additionally, RB/Rb loss altered mitochondrial pyruvate oxidation from (13)C-glucose through the TCA cycle in mouse tissues and cultured cells. Consequently, RB(KO) cells have an enhanced sensitivity to mitochondrial stress conditions. In summary, proteomic analyses provide a new perspective on Rb/RB1 mutation, highlighting the importance of pRb for mitochondrial function and suggesting vulnerabilities for treatment.

journal_name

Genes Dev

journal_title

Genes & development

authors

Nicolay BN,Danielian PS,Kottakis F,Lapek JD Jr,Sanidas I,Miles WO,Dehnad M,Tschöp K,Gierut JJ,Manning AL,Morris R,Haigis K,Bardeesy N,Lees JA,Haas W,Dyson NJ

doi

10.1101/gad.264127.115

subject

Has Abstract

pub_date

2015-09-01 00:00:00

pages

1875-89

issue

17

eissn

0890-9369

issn

1549-5477

pii

gad.264127.115

journal_volume

29

pub_type

杂志文章

相关文献

GENES & DEVELOPMENT文献大全
  • Control of a neuronal morphology program by an RNA-binding zinc finger protein, Unkempt.

    abstract：:Cellular morphology is an essential determinant of cellular function in all kingdoms of life, yet little is known about how cell shape is controlled. Here we describe a molecular program that controls the early morphology of neurons through a metazoan-specific zinc finger protein, Unkempt. Depletion of Unkempt in mous...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.258483.115

    authors： Murn J,Zarnack K,Yang YJ,Durak O,Murphy EA,Cheloufi S,Gonzalez DM,Teplova M,Curk T,Zuber J,Patel DJ,Ule J,Luscombe NM,Tsai LH,Walsh CA,Shi Y

    更新日期：2015-03-01 00:00:00

  • Sorting out adipocyte precursors and their role in physiology and disease.

    abstract：:The ability to maintain and expand the pool of adipocytes in adults is integral to the regulation of energy balance, tissue/stem cell homeostasis, and disease pathogenesis. For decades, our knowledge of adipocyte precursors has relied on cellular models. The identity of native adipocyte precursors has remained unclear...

    journal_title：Genes & development

    pub_type： 杂志文章,评审

    doi：10.1101/gad.293704.116

    authors： Hepler C,Vishvanath L,Gupta RK

    更新日期：2017-01-15 00:00:00

  • Negative feedback maintenance of heme homeostasis by its receptor, Rev-erbalpha.

    abstract：:Intracellular heme levels must be tightly regulated to maintain proper mitochondrial respiration while minimizing toxicity, but the homeostatic mechanisms are not well understood. Here we report a novel negative feedback mechanism whereby the nuclear heme receptor Rev-erbalpha tightly controls the level of its own lig...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.1825809

    authors： Wu N,Yin L,Hanniman EA,Joshi S,Lazar MA

    更新日期：2009-09-15 00:00:00

  • The flagellar-specific transcription factor, sigma28, is the Type III secretion chaperone for the flagellar-specific anti-sigma28 factor FlgM.

    abstract：:The sigma(28) protein is a member of the bacterial sigma(70)-family of transcription factors that directs RNA polymerase to flagellar late (class 3) promoters. The sigma(28) protein is regulated in response to flagellar assembly by the anti-sigma(28) factor FlgM. FlgM inhibits sigma(28)-dependent transcription of gene...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.380406

    authors： Aldridge PD,Karlinsey JE,Aldridge C,Birchall C,Thompson D,Yagasaki J,Hughes KT

    更新日期：2006-08-15 00:00:00

  • Role of the Escherichia coli RecQ DNA helicase in SOS signaling and genome stabilization at stalled replication forks.

    abstract：:The RecQ protein family is a highly conserved group of DNA helicases that play roles in maintaining genomic stability. In this study, we present biochemical and genetic evidence that Escherichia coli RecQ processes stalled replication forks and participates in SOS signaling. Cells that carry dnaE486, a mutation in the...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.1223804

    authors： Hishida T,Han YW,Shibata T,Kubota Y,Ishino Y,Iwasaki H,Shinagawa H

    更新日期：2004-08-01 00:00:00

  • Life on the edge: telomeres and persistent DNA breaks converge at the nuclear periphery.

    abstract：:Persistent DNA double-strand breaks and telomeres represent genomic hazards, as they can instigate inappropriate repair reactions. Two recent papers by Oza and colleagues (pp. 912-917) and Schober and colleagues (pp. 928-938) show that both types of DNA ends are sequestered from bulk DNA by Mps3, a SUN domain protein ...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.1805309

    authors： Gartenberg MR

    更新日期：2009-05-01 00:00:00

  • Restriction of the activity of the recombination site dif to a small zone of the Escherichia coli chromosome.

    abstract：:The recombination site dif is the target on the Escherichia coli chromosome of the site-specific recombinases XerC and XerD. The dif/XerC-D system plays a role during the cell cycle, probably by favoring sister chromosome monomerization or separation. A phenomenon of regional control over dif activity, also analyzed i...

    journal_title：Genes & development

    pub_type： 评论,杂志文章

    doi：10.1101/gad.10.9.1152

    authors： Cornet F,Louarn J,Patte J,Louarn JM

    更新日期：1996-05-01 00:00:00

  • Isolation of a cDNA encoding the largest subunit of TFIIA reveals functions important for activated transcription.

    abstract：:Transcription factor IIA has been shown to interact with the TATA-binding protein and to act early during preinitiation complex formation. The human factor is composed of three subunits (alpha, beta, gamma). A human cDNA clone encoding the largest subunit of TFIIA (alpha) was isolated. The recombinant alpha polypeptid...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.7.11.2246

    authors： Ma D,Watanabe H,Mermelstein F,Admon A,Oguri K,Sun X,Wada T,Imai T,Shiroya T,Reinberg D

    更新日期：1993-11-01 00:00:00

  • Transabdominal, a dominant mutant of the Bithorax Complex, produces a sexually dimorphic segmental transformation in Drosophila.

    abstract：:Transabdominal (Tab), a dominant mutation in the Bithorax Complex (BX-C) of Drosophila, creates a sexually dimorphic pattern of segmental transformation that has complete penetrance and expressivity. Specific regions within the notum of the second thoracic segment (T2) are transformed into abdominal-like cuticle; thus...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.1.2.111

    authors： Celniker SE,Lewis EB

    更新日期：1987-04-01 00:00:00

  • Cas6 is an endoribonuclease that generates guide RNAs for invader defense in prokaryotes.

    abstract：:An RNA-based gene silencing pathway that protects bacteria and archaea from viruses and other genome invaders is hypothesized to arise from guide RNAs encoded by CRISPR loci and proteins encoded by the cas genes. CRISPR loci contain multiple short invader-derived sequences separated by short repeats. The presence of v...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.1742908

    authors： Carte J,Wang R,Li H,Terns RM,Terns MP

    更新日期：2008-12-15 00:00:00

  • Inhibition of apoptosis by ATFx: a novel role for a member of the ATF/CREB family of mammalian bZIP transcription factors.

    abstract：:The mammalian ATF/CREB family of transcription factors comprises a large group of basic-region leucine zipper (bZIP) proteins whose members mediate diverse transcriptional regulatory functions. Here we report that expression of a specific mouse ATF gene, ATFx, is down-regulated in a variety of cells undergoing apoptos...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.992202

    authors： Persengiev SP,Devireddy LR,Green MR

    更新日期：2002-07-15 00:00:00

  • Against the oxidative damage theory of aging: superoxide dismutases protect against oxidative stress but have little or no effect on life span in Caenorhabditis elegans.

    abstract：:The superoxide radical (O(2)(-)) has long been considered a major cause of aging. O(2)(-) in cytosolic, extracellular, and mitochondrial pools is detoxified by dedicated superoxide dismutase (SOD) isoforms. We tested the impact of each SOD isoform in Caenorhabditis elegans by manipulating its five sod genes and saw no...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.504808

    authors： Doonan R,McElwee JJ,Matthijssens F,Walker GA,Houthoofd K,Back P,Matscheski A,Vanfleteren JR,Gems D

    更新日期：2008-12-01 00:00:00

  • PPARγ is a nexus controlling alternative activation of macrophages via glutamine metabolism.

    abstract：:The nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) is known to regulate lipid metabolism in many tissues, including macrophages. Here we report that peritoneal macrophage respiration is enhanced by rosiglitazone, an activating PPARγ ligand, in a PPARγ-dependent manner. Moreover, PPARγ is require...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.312355.118

    authors： Nelson VL,Nguyen HCB,Garcìa-Cañaveras JC,Briggs ER,Ho WY,DiSpirito JR,Marinis JM,Hill DA,Lazar MA

    更新日期：2018-08-01 00:00:00

  • The nonspecific DNA-binding and -bending proteins HMG1 and HMG2 promote the assembly of complex nucleoprotein structures.

    abstract：:The mammalian high mobility group proteins HMG1 and HMG2 are abundant, chromatin-associated proteins whose cellular function is not known. In this study we show that these proteins can substitute for the prokaryotic DNA-bending protein HU in promoting the assembly of the Hin invertasome, an intermediate structure in H...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.7.8.1521

    authors： Paull TT,Haykinson MJ,Johnson RC

    更新日期：1993-08-01 00:00:00

  • sel-10, a negative regulator of lin-12 activity in Caenorhabditis elegans, encodes a member of the CDC4 family of proteins.

    abstract：:Mutations that influence lin-12 activity in Caenorhabditis elegans may identify conserved factors that regulate the activity of lin-12/Notch proteins. We describe genetic evidence indicating that sel-10 is a negative regulator of lin-12/Notch-mediated signaling in C. elegans. Sequence analysis shows that SEL-10 is a m...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.11.23.3182

    authors： Hubbard EJ,Wu G,Kitajewski J,Greenwald I

    更新日期：1997-12-01 00:00:00

  • Runx1 prevents wasting, myofibrillar disorganization, and autophagy of skeletal muscle.

    abstract：:Disruptions in the use of skeletal muscle lead to muscle atrophy. After short periods of disuse, muscle atrophy is reversible, and even after prolonged periods of inactivity, myofiber degeneration is uncommon. The pathways that regulate atrophy, initiated either by peripheral nerve damage, immobilization, aging, catab...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.1318305

    authors： Wang X,Blagden C,Fan J,Nowak SJ,Taniuchi I,Littman DR,Burden SJ

    更新日期：2005-07-15 00:00:00

  • Transcript levels and translational control of hsp70 synthesis in Xenopus oocytes.

    abstract：:Until recently it was believed that Xenopus oocytes respond to heat shock by synthesizing the 70-kD heat shock protein hsp70 and that, uniquely amongst animal cell types, this response is mediated entirely at the translational level. This view has now been challenged and we present data that reevaluate the involvement...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.1.5.433

    authors： Horrell A,Shuttleworth J,Colman A

    更新日期：1987-07-01 00:00:00

  • A conserved ncRNA-binding protein recruits silencing factors to heterochromatin through an RNAi-independent mechanism.

    abstract：:Long noncoding RNAs (lncRNAs) can trigger repressive chromatin, but how they recruit silencing factors remains unclear. In Schizosaccharomyces pombe, heterochromatin assembly on transcribed noncoding pericentromeric repeats requires both RNAi and RNAi-independent mechanisms. In Saccharomyces cerevisiae, which lacks a ...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.226019.113

    authors： Marina DB,Shankar S,Natarajan P,Finn KJ,Madhani HD

    更新日期：2013-09-01 00:00:00

  • Dorsal and neural expression of a tyrosine kinase-related Drosophila gene during embryonic development.

    abstract：:Sequence analysis of an embryonic transcript of Drosophila predicts a tyrosine protein kinase-related gene. The prediction is based on several protein domains that are homologous to the functional domains of kinase-related oncogenes and several serine, threonine, and tyrosine protein kinases. For this reason, we named...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.1.8.862

    authors： Haller J,Côté S,Brönner G,Jäckle H

    更新日期：1987-10-01 00:00:00

  • Replication initiates at a confined region during DNA amplification in Sciara DNA puff II/9A.

    abstract：:Two independent two-dimensional (2D) gel methods were used to map an origin of replication that is developmentally regulated by the steroid hormone ecdysone, namely an origin for DNA puff amplification in the fungus fly Sciara coprophila. Initiation of replication was found to occur within a small region of no larger ...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.7.6.1072

    authors： Liang C,Spitzer JD,Smith HS,Gerbi SA

    更新日期：1993-06-01 00:00:00

  • Ferredoxin reductase is critical for p53-dependent tumor suppression via iron regulatory protein 2.

    abstract：:Ferredoxin reductase (FDXR), a target of p53, modulates p53-dependent apoptosis and is necessary for steroidogenesis and biogenesis of iron-sulfur clusters. To determine the biological function of FDXR, we generated a Fdxr-deficient mouse model and found that loss of Fdxr led to embryonic lethality potentially due to ...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.299388.117

    authors： Zhang Y,Qian Y,Zhang J,Yan W,Jung YS,Chen M,Huang E,Lloyd K,Duan Y,Wang J,Liu G,Chen X

    更新日期：2017-06-15 00:00:00

  • A thymus-specific member of the HMG protein family regulates the human T cell receptor C alpha enhancer.

    abstract：:The human T cell-specific transcription factor TCF-1 alpha plays a key role in the tissue-specific activation of the T cell receptor (TCR) C alpha enhancer and binds to pyrimidine-rich elements (5'-PyCTTTG-3') present in a variety of other T cell-specific control regions. Using amino acid sequence information derived ...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.5.4.656

    authors： Waterman ML,Fischer WH,Jones KA

    更新日期：1991-04-01 00:00:00

  • The DAF-3 Smad protein antagonizes TGF-beta-related receptor signaling in the Caenorhabditis elegans dauer pathway.

    abstract：:Signals from TGF-beta superfamily receptors are transduced to the nucleus by Smad proteins, which transcriptionally activate target genes. In Caenorhabditis elegans, defects in a TGF-beta-related pathway cause a reversible developmental arrest and metabolic shift at the dauer larval stage. Null mutations in daf-3 supp...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.11.20.2679

    authors： Patterson GI,Koweek A,Wong A,Liu Y,Ruvkun G

    更新日期：1997-10-15 00:00:00

  • eIF2 independently binds two distinct eIF2B subcomplexes that catalyze and regulate guanine-nucleotide exchange.

    abstract：:eIF2B is a heteropentameric guanine-nucleotide exchange factor essential for protein synthesis initiation in eukaryotes. Its activity is inhibited in response to starvation or stress by phosphorylation of the alpha subunit of its substrate, translation initiation factor eIF2, resulting in reduced rates of translation ...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.12.4.514

    authors： Pavitt GD,Ramaiah KV,Kimball SR,Hinnebusch AG

    更新日期：1998-02-15 00:00:00

  • MIM/BEG4, a Sonic hedgehog-responsive gene that potentiates Gli-dependent transcription.

    abstract：:Sonic hedgehog (Shh) signaling plays a critical role during development and carcinogenesis. While Gli family members govern the transcriptional output of Shh signaling, little is known how Gli-mediated transcriptional activity is regulated. Here we identify the actin-binding protein Missing in Metastasis (MIM) as a ne...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.1221804

    authors： Callahan CA,Ofstad T,Horng L,Wang JK,Zhen HH,Coulombe PA,Oro AE

    更新日期：2004-11-15 00:00:00

  • TopBP1 activates ATR through ATRIP and a PIKK regulatory domain.

    abstract：:The ATR (ATM and Rad3-related) kinase and its regulatory partner ATRIP (ATR-interacting protein) coordinate checkpoint responses to DNA damage and replication stress. TopBP1 functions as a general activator of ATR. However, the mechanism by which TopBP1 activates ATR is unknown. Here, we show that ATRIP contains a Top...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.1666208

    authors： Mordes DA,Glick GG,Zhao R,Cortez D

    更新日期：2008-06-01 00:00:00

  • Polycomb-mediated repression during terminal differentiation: what don't you want to be when you grow up?

    abstract：:Chromatin-modifying enzymes are known to be critical components for the correct differentiation of embryonic stem cells into specific lineages, such as neurons. Recently, the role of Polycomb group proteins has been studied in the specification and differentiation of muscle stem cells. In this perspective, we review a...

    journal_title：Genes & development

    pub_type： 评论,杂志文章

    doi：10.1101/gad.2054311

    authors： Conerly ML,MacQuarrie KL,Fong AP,Yao Z,Tapscott SJ

    更新日期：2011-05-15 00:00:00

  • Snail blocks the cell cycle and confers resistance to cell death.

    abstract：:The Snail zinc-finger transcription factors trigger epithelial-mesenchymal transitions (EMTs), endowing epithelial cells with migratory and invasive properties during both embryonic development and tumor progression. During EMT, Snail provokes the loss of epithelial markers, as well as changes in cell shape and the ex...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.294104

    authors： Vega S,Morales AV,Ocaña OH,Valdés F,Fabregat I,Nieto MA

    更新日期：2004-05-15 00:00:00

  • Activation of Rac1 by a Crk SH3-binding protein, DOCK180.

    abstract：:DOCK180 is involved in integrin signaling through CrkII-p130(Cas) complexes. We have studied the involvement of DOCK180 in Rac1 signaling cascades. DOCK180 activated JNK in a manner dependent on Rac1, Cdc42Hs, and SEK, and overexpression of DOCK180 increased the amount of GTP-bound Rac1 in 293T cells. Coexpression of ...

    journal_title：Genes & development

    pub_type： 杂志文章

    doi：10.1101/gad.12.21.3331

    authors： Kiyokawa E,Hashimoto Y,Kobayashi S,Sugimura H,Kurata T,Matsuda M

    更新日期：1998-11-01 00:00:00

  • Nitric oxide directly regulates gene expression during Drosophila development: need some gas to drive into metamorphosis?

    abstract：:Nitric oxide (NO) is an important second messenger involved in numerous biological processes, but how it regulates gene expression is not well understood. In this issue of Genes & Development, Cáceres and colleagues (pp. 1476-1485) report a critical requirement of NO as a direct regulator of gene expression through it...

    journal_title：Genes & development

    pub_type： 评论,杂志文章

    doi：10.1101/gad.2080411

    authors： Yamanaka N,O'Connor MB

    更新日期：2011-07-15 00:00:00