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4E-BP1 (53H11) Rabbit mAb antibody

RRID:AB_10691384

Antibody ID

AB_2097841

Target Antigen

4E-BP1 (53H11) Rabbit mAb h, m, r, mk, human, mouse, non-human primate, rat

Proper Citation

(Cell Signaling Technology Cat# 9644, RRID:AB_2097841)

Clonality

monoclonal antibody

Comments

Applications: W, IP, IHC-P, IF-IC, F. Consolidation: AB_10691384, AB_10830220.

Host Organism

rabbit

Vendor

Cell Signaling Technology

Cat Num

9644 also 9644S, 9644P

Publications that use this research resource

Cancer Cells Co-opt the Neuronal Redox-Sensing Channel TRPA1 to Promote Oxidative-Stress Tolerance.

  • Takahashi N
  • Cancer Cell
  • 2018 Jun 11

Literature context:


Abstract:

Cancer cell survival is dependent on oxidative-stress defenses against reactive oxygen species (ROS) that accumulate during tumorigenesis. Here, we show a non-canonical oxidative-stress defense mechanism through TRPA1, a neuronal redox-sensing Ca2+-influx channel. In TRPA1-enriched breast and lung cancer spheroids, TRPA1 is critical for survival of inner cells that exhibit ROS accumulation. Moreover, TRPA1 promotes resistance to ROS-producing chemotherapies, and TRPA1 inhibition suppresses xenograft tumor growth and enhances chemosensitivity. TRPA1 does not affect redox status but upregulates Ca2+-dependent anti-apoptotic pathways. NRF2, an oxidant-defense transcription factor, directly controls TRPA1 expression, thus providing an orthogonal mechanism for protection against oxidative stress together with canonical ROS-neutralizing mechanisms. These findings reveal an oxidative-stress defense program involving TRPA1 that could be exploited for targeted cancer therapies.

Funding information:
  • NCRR NIH HHS - C06 RR030414(United States)

Pseudouridylation of tRNA-Derived Fragments Steers Translational Control in Stem Cells.

  • Guzzi N
  • Cell
  • 2018 May 17

Literature context:


Abstract:

Pseudouridylation (Ψ) is the most abundant and widespread type of RNA epigenetic modification in living organisms; however, the biological role of Ψ remains poorly understood. Here, we show that a Ψ-driven posttranscriptional program steers translation control to impact stem cell commitment during early embryogenesis. Mechanistically, the Ψ "writer" PUS7 modifies and activates a novel network of tRNA-derived small fragments (tRFs) targeting the translation initiation complex. PUS7 inactivation in embryonic stem cells impairs tRF-mediated translation regulation, leading to increased protein biosynthesis and defective germ layer specification. Remarkably, dysregulation of this posttranscriptional regulatory circuitry impairs hematopoietic stem cell commitment and is common to aggressive subtypes of human myelodysplastic syndromes. Our findings unveil a critical function of Ψ in directing translation control in stem cells with important implications for development and disease.

Funding information:
  • NIDDK NIH HHS - DK068164(United States)

LARP1 functions as a molecular switch for mTORC1-mediated translation of an essential class of mRNAs.

  • Hong S
  • Elife
  • 2017 Jun 26

Literature context:


Abstract:

The RNA binding protein, LARP1, has been proposed to function downstream of mTORC1 to regulate the translation of 5'TOP mRNAs such as those encoding ribosome proteins (RP). However, the roles of LARP1 in the translation of 5'TOP mRNAs are controversial and its regulatory roles in mTORC1-mediated translation remain unclear. Here we show that LARP1 is a direct substrate of mTORC1 and Akt/S6K1. Deep sequencing of LARP1-bound mRNAs reveal that non-phosphorylated LARP1 interacts with both 5' and 3'UTRs of RP mRNAs and inhibits their translation. Importantly, phosphorylation of LARP1 by mTORC1 and Akt/S6K1 dissociates it from 5'UTRs and relieves its inhibitory activity on RP mRNA translation. Concomitantly, phosphorylated LARP1 scaffolds mTORC1 on the 3'UTRs of translationally-competent RP mRNAs to facilitate mTORC1-dependent induction of translation initiation. Thus, in response to cellular mTOR activity, LARP1 serves as a phosphorylation-sensitive molecular switch for turning off or on RP mRNA translation and subsequent ribosome biogenesis.

Funding information:
  • NIDDK NIH HHS - R01 DK083491()
  • NIGMS NIH HHS - R01 GM088565()
  • NIGMS NIH HHS - R01 GM110019()

Clock Regulation of Metabolites Reveals Coupling between Transcription and Metabolism.

  • Krishnaiah SY
  • Cell Metab.
  • 2017 Apr 4

Literature context:


Abstract:

The intricate connection between the circadian clock and metabolism remains poorly understood. We used high temporal resolution metabolite profiling to explore clock regulation of mouse liver and cell-autonomous metabolism. In liver, ∼50% of metabolites were circadian, with enrichment of nucleotide, amino acid, and methylation pathways. In U2 OS cells, 28% were circadian, including amino acids and NAD biosynthesis metabolites. Eighteen metabolites oscillated in both systems and a subset of these in primary hepatocytes. These 18 metabolites were enriched in methylation and amino acid pathways. To assess clock dependence of these rhythms, we used genetic perturbation. BMAL1 knockdown diminished metabolite rhythms, while CRY1 or CRY2 perturbation generally shortened or lengthened rhythms, respectively. Surprisingly, CRY1 knockdown induced 8 hr rhythms in amino acid, methylation, and vitamin metabolites, decoupling metabolite from transcriptional rhythms, with potential impact on nutrient sensing in vivo. These results provide the first comprehensive views of circadian liver and cell-autonomous metabolism.

Funding information:
  • NCATS NIH HHS - UL1 TR000003()
  • NCI NIH HHS - F32 CA180370()
  • NCI NIH HHS - K99 CA204593()
  • NCI NIH HHS - P30 CA016086()
  • NCI NIH HHS - R01 CA057341()
  • NIA NIH HHS - R01 AG043483()
  • NIDDK NIH HHS - R01 DK098656()
  • NINDS NIH HHS - R01 NS054794()

Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.

  • Tărlungeanu DC
  • Cell
  • 2016 Dec 1

Literature context:


Abstract:

Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. We previously described abnormalities in the branched-chain amino acid (BCAA) catabolic pathway as a cause of ASD. Here, we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation, and severe neurological abnormalities. Furthermore, we identified several patients with autistic traits and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. Finally, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for the BCAA in human brain function.

Funding information:
  • NIMH NIH HHS - R01 MH064043(United States)