Twist is a potential oncogene that inhibits apoptosis

Maestro, R., Dei Tos, A. P., Hamamori, Y., Krasnokutsky, S., Sartorelli, V., Kedes, L., Doglioni, C., Beach, D. H., Hannon, G. J. (September 1999) Twist is a potential oncogene that inhibits apoptosis. Genes and Development, 13 (17). pp. 2207-17. ISSN 0890-9369

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URL: https://www.ncbi.nlm.nih.gov/pubmed/10485844
DOI: 10.1101/gad.13.17.2207

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 Dermo1. 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.

Item Type: Paper
Uncontrolled Keywords: Animals Apoptosis Cell Division Cell Line Cell Transformation Neoplastic Fibroblasts Gene Deletion Genes myc Genes p53 Genes ras Helix Loop Helix Motifs Humans Mice Nuclear Proteins Oncogenes Rats Repressor Proteins Rhabdomyosarcoma genetics Transcription Factors genetics metabolism Tumor Suppressor Protein p53 metabolism Twist Transcription Factor
Subjects: diseases & disorders > cancer
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > apoptosis
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > cDNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene silencing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > oncogene
CSHL Authors:
Communities: CSHL labs > Hannon lab
Depositing User: Editor Margaret Fantz
Date: 1 September 1999
Date Deposited: 17 Apr 2012 16:56
Last Modified: 01 Dec 2016 17:15
PMCID: PMC317004
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26119

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