Related Experiment Video

Updated: May 30, 2026

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans
08:12

Identification of EGFR and RAS Inhibitors using Caenorhabditis elegans

Published on: October 5, 2020

3'UTR elements inhibit Ras-induced C/EBPβ post-translational activation and senescence in tumour cells

Sandip K Basu1, Radek Malik, Christopher J Huggins

  • 1Laboratory of Cancer Prevention, Center for Cancer Research, National Cancer Institute-Frederick, NIH, MD, USA.

The EMBO Journal
|August 2, 2011
PubMed

Insights

The 3' untranslated region (3'UTR) of C/EBPβ mRNA suppresses its activation in cancer cells by sequestering it away from signaling pathways. This mechanism prevents anti-oncogenic functions, unlike in primary cells where C/EBPβ promotes senescence.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Cancer Research

Background:

  • CCAAT-enhancer-binding protein beta (C/EBPβ) is activated by Ras-MEK-ERK signaling and is crucial for oncogene-induced senescence (OIS) in fibroblasts.
  • C/EBPβ also exhibits pro-oncogenic functions in various tumor cells, suggesting complex regulatory mechanisms.
  • Understanding how C/EBPβ activity is differentially regulated in normal versus cancer cells is critical for cancer therapy.

Purpose of the Study:

  • To investigate the role of the 3' untranslated region (3'UTR) of C/EBPβ mRNA in regulating its activation by H-Ras(V12).
  • To elucidate the mechanism by which 3'UTR sequences suppress C/EBPβ activity and its anti-oncogenic functions in immortalized/transformed cells.
  • To determine the impact of 3'UTR-mediated regulation on senescence induction and cancer-related gene expression.

Main Methods:

  • Utilized immortalized/transformed cell lines and primary fibroblasts.
  • Investigated the effects of H-Ras(V12) expression on C/EBPβ activity, including DNA binding, transactivation, phosphorylation, and homodimerization.
  • Analyzed the role of the C/EBPβ 3'UTR, AU-rich elements (AREs), and the RNA-binding protein HuR in regulating C/EBPβ function and mRNA localization.
  • Assessed the expression of senescence-associated and cancer-related target genes.

Main Results:

  • The C/EBPβ 3'UTR significantly inhibited Ras-induced C/EBPβ activity (cytostatic effects, DNA binding, transactivation, phosphorylation, homodimerization) in immortalized/transformed cells, but not in primary cells.
  • The 3'UTR suppressed senescence-associated gene induction while promoting cancer-related and TGFβ signaling genes.
  • AU-rich elements (AREs) and HuR were essential for 3'UTR-mediated inhibition and excluded Cebpb mRNA from activated ERK1/2-containing perinuclear regions.
  • Primary fibroblasts lacked 3'UTR inhibition, allowing Ras-induced C/EBPβ activation and OIS.

Conclusions:

  • Non-coding mRNA sequences, specifically the 3'UTR of C/EBPβ, provide a novel regulatory mechanism controlling C/EBPβ activity.
  • The 3'UTR selectively suppresses the anti-oncogenic functions of C/EBPβ in cancer cells by regulating its translation site and interaction with signaling pathways.
  • This differential regulation by the 3'UTR contributes to the distinct roles of C/EBPβ in senescence versus cancer progression.

More Related Videos

In Vivo Detection and Analysis of Rb Protein SUMOylation in Human Cells09:40

In Vivo Detection and Analysis of Rb Protein SUMOylation in Human Cells

Published on: November 2, 2017

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

Related Concept Videos

The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...