ATF2 - at the crossroad of nuclear and cytosolic functions

Eric Lau, Ze'ev A. Ronai

Research output: Contribution to journalEditorial

79 Scopus citations

Abstract

An increasing number of transcription factors have been shown to elicit oncogenic and tumor suppressor activities, depending on the tissue and cell context. Activating transcription factor 2 (ATF2; also known as cAMP-dependent transcription factor ATF-2) has oncogenic activities in melanoma and tumor suppressor activities in non-malignant skin tumors and breast cancer. Recent work has shown that the opposing functions of ATF2 are associated with its subcellular localization. In the nucleus, ATF2 contributes to global transcription and the DNA damage response, in addition to specific transcriptional activities that are related to cell development, proliferation and death. ATF2 can also translocate to the cytosol, primarily following exposure to severe genotoxic stress, where it impairs mitochondrial membrane potential and promotes mitochondrial-based cell death. Notably, phosphorylation of ATF2 by the epsilon isoform of protein kinase C (PKCe) is the master switch that controls its subcellular localization and function. Here, we summarize our current understanding of the regulation and function of ATF2 in both subcellular compartments. This mechanism of control of a non-genetically modified transcription factor represents a novel paradigm for 'oncogene addiction'.

Original languageEnglish
Pages (from-to)2815-2824
Number of pages10
JournalJournal of Cell Science
Volume125
Issue number12
DOIs
StatePublished - 15 Jun 2012
Externally publishedYes

Keywords

  • ATF2
  • DNA damage
  • JNK
  • Melanoma
  • Mitochondria
  • P38 MAPK
  • PKC
  • Skin cancer
  • Transcription

Fingerprint

Dive into the research topics of 'ATF2 - at the crossroad of nuclear and cytosolic functions'. Together they form a unique fingerprint.

Cite this