Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

C-myc-mediated regulation of telomerase activity is disabled in immortalized cells

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Drissi, R.
  • Zindy, F.
  • Roussel, M. F.
  • Cleveland, John

publication date

  • August 2001

journal

  • Journal of Biological Chemistry  Journal

abstract

  • Myc overexpression is a hallmark of human cancer and promotes transformation by facilitating immortalization. This function has been linked to the ability of c-Myc to induce the expression of the catalytic subunit of telomerase, telomerase reverse transcriptase (TERT), as ectopic expression of TERT immortalizes some primary human cell types. c-Myc up-regulates telomerase activity in primary mouse embryonic fibroblasts (MEFs) and myeloid cells. Paradoxically, Myc overexpression also triggers the ARF-p53 apoptotic program, which is activated when MEFs undergo replicative crises following culture ex vivo. The rare immortal variants that arise from these cultures generally suffer mutations in p53 or delete Ink4a/ARF, and Myc greatly increases the frequency of these events. Alternative reading frame (ARF)- and p53-null MEFs have increased telomerase activity, as do variant immortal clones that bypass replicative crisis. Similarly, immortal murine NIH-3T3 fibroblasts and myeloid 32D.3 and FDC-P1.2 cells do not express ARF and have robust telomerase activity. However, Myc overexpression in these immortal cells results in remarkably discordant regulation of TERT and telomerase activity. Furthermore, in MEFs and 32D.3 cells TERT expression and telomerase activity are regulated independently of endogenous c-Myc. Thus, the regulation of TERT and telomerase activity is complex and is also regulated by factors other than Myc, ARF, or p53.

subject areas

  • 3T3 Cells
  • Animals
  • Apoptosis
  • Blotting, Western
  • Cell Line
  • Cells, Cultured
  • Down-Regulation
  • Fibroblasts
  • Humans
  • Mice
  • Mutation
  • Proto-Oncogene Proteins c-myc
  • Reading Frames
  • Reverse Transcriptase Polymerase Chain Reaction
  • Telomerase
  • Time Factors
  • Transcription, Genetic
  • Up-Regulation
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M101899200

PubMed ID

  • 11402027
scroll to property group menus

Additional Document Info

start page

  • 29994

end page

  • 30001

volume

  • 276

issue

  • 32

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support