twist is a potential oncogene that inhibits apoptosis

Roberta Maestro, Angelo P. Dei Tos, Yasuo Hamamori, Svetlana Krasnokutsky, Vittorio Sartorelli, Larry Kedes, Claudio Doglioni, David H. Beach, Gregory J. Hannon

Research output: Contribution to journalArticle

Abstract

Oncogene activation increases susceptibility to apoptosis. Thus, tumorigenesis must depend, in part, on compensating mutations that protect from programmed cell death. A functional screen for cDNAs that could counteract the proapoptotic effects of the myc oncogene identified two related bHLH family members, Twist and Dermol. Both of these proteins inhibited oncogene- and p53-dependent cell death. Twist expression bypassed p53-induced growth arrest. These effects correlated with an ability of Twist to interfere with activation of a p53-dependent reporter and to impair induction of p53 target genes in response to DNA damage. An underlying explanation for this observation may be provided by the ability of Twist to reduce expression of the ARF tumor suppressor. Thus, Twist may affect p53 indirectly through modulation of the ARF/MDM2/p53 pathway. Consistent with a role as a potential oncoprotein, Twist expression promoted colony formation of E1A/ras-transformed mouse embryo fibroblasts (MEFs) in soft agar. Furthermore, Twist was inappropriately expressed in 50% of rhabdomyosarcomas, a tumor that arises from skeletal muscle precursors that fail to differentiate. Twist is known to block myogenic differentiation. Thus, Twist may play multiple roles in the formation of rhabdomyosarcomas, halting terminal differentiation, inhibiting apoptosis, and interfering with the p53 tumor-suppressor pathway.

Original languageEnglish
Pages (from-to)2207-2217
Number of pages11
JournalGenes and Development
Volume13
Issue number17
DOIs
Publication statusPublished - Sep 1 1999

Keywords

  • Apoptosis
  • Dermol
  • Oncogenes
  • Tumorigenesis
  • Twist

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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    Maestro, R., Dei Tos, A. P., Hamamori, Y., Krasnokutsky, S., Sartorelli, V., Kedes, L., Doglioni, C., Beach, D. H., & Hannon, G. J. (1999). twist is a potential oncogene that inhibits apoptosis. Genes and Development, 13(17), 2207-2217. https://doi.org/10.1101/gad.13.17.2207