Pim-1 protein expression is regulated by its 5'-untranslated region and translation initiation factor elF-4E.

Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research · 1997 · Unclear · Insufficient evidence

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UnclearInsufficient evidencePaper 4156

Study snapshot

PublicationCell growth & differentiation : the molecular biology journal of the American Association for Cancer Research · 1997

Study typeother

Reported directionUnclear

Evidence ratingInsufficient

Abstract

Expression of Pim-1, an oncogenic serine/threonine kinase, is highly regulated at the transcriptional, posttranscriptional, and posttranslational levels. Here, we report that expression of Pim-1 kinase is additionally regulated at the translational level. Pim-1 protein expression did not increase in Hut-78 lymphocytes in response to PMA1/ionomycin stimulation despite approximately 20-fold increases in mRNA levels, suggesting that translation was repressed. Sequence analysis of the 5'-untranslated region (UTR) indicated a long (400 nucleotide), 76% G + C-rich region, characteristics known to inhibit translation. Deletion of the 5'-UTR of pim-1 increased translation of the Pim-1 protein approximately 10-fold in vitro in reticulocyte lysates and approximately 1.6-fold in vivo in NIH-3T3 cells. When full-length 5'-UTR-containing pim-1 cDNA constructs were transfected into NIH-3T3 cells overexpressing eukaryotic translation initiation factor 4E (eIF-4E), approximately 6-fold higher levels of Pim-1 protein were produced, as compared to that produced in control NIH-3T3 cells. Moreover, eIF-4E overexpression had little effect in the absence of the 5'-UTR, suggesting that it relieved 5'-UTR-mediated inhibition of Pim-1 expression.

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Study typeother

Effect directionunclear

PopulationNot supplied

Sample sizeNot supplied

ExposureNot supplied

Evidence strengthInsufficientConfidence: 74% · Peer reviewed: yes

Main findings

In Hut-78 lymphocytes, Pim-1 protein expression did not increase after PMA/ionomycin stimulation despite ~20-fold increases in Pim-1 mRNA, suggesting translational repression. Deleting the Pim-1 5'-UTR increased translation ~10-fold in vitro (reticulocyte lysates) and ~1.6-fold in vivo (NIH-3T3 cells). In NIH-3T3 cells overexpressing eIF-4E, full-length 5'-UTR-containing Pim-1 constructs produced ~6-fold higher Pim-1 protein than controls, while eIF-4E had little effect without the 5'-UTR, consistent with relief of 5'-UTR-mediated inhibition.

Outcomes measured

Pim-1 protein expression/translation
Effect of Pim-1 5'-UTR on translation
Effect of eIF-4E overexpression on Pim-1 protein levels

View raw extracted JSON

{
  "study_type": "other",
  "exposure": {
    "band": null,
    "source": null,
    "frequency_mhz": null,
    "sar_wkg": null,
    "duration": null
  },
  "population": null,
  "sample_size": null,
  "outcomes": [
    "Pim-1 protein expression/translation",
    "Effect of Pim-1 5'-UTR on translation",
    "Effect of eIF-4E overexpression on Pim-1 protein levels"
  ],
  "main_findings": "In Hut-78 lymphocytes, Pim-1 protein expression did not increase after PMA/ionomycin stimulation despite ~20-fold increases in Pim-1 mRNA, suggesting translational repression. Deleting the Pim-1 5'-UTR increased translation ~10-fold in vitro (reticulocyte lysates) and ~1.6-fold in vivo (NIH-3T3 cells). In NIH-3T3 cells overexpressing eIF-4E, full-length 5'-UTR-containing Pim-1 constructs produced ~6-fold higher Pim-1 protein than controls, while eIF-4E had little effect without the 5'-UTR, consistent with relief of 5'-UTR-mediated inhibition.",
  "effect_direction": "unclear",
  "limitations": [],
  "evidence_strength": "insufficient",
  "confidence": 0.74,
  "peer_reviewed_likely": "yes",
  "keywords": [
    "Pim-1",
    "5'-untranslated region",
    "translation regulation",
    "eIF-4E",
    "NIH-3T3",
    "Hut-78",
    "reticulocyte lysate",
    "PMA",
    "ionomycin"
  ],
  "suggested_hubs": []
}

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AI-extracted fields are generated from the abstract and metadata and may be incomplete or incorrect. This material is for informational purposes and is not medical advice.

Identifiers and source

DOI: Not supplied
PubMed: 9419425

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