RGD Reference Report - Myc suppresses induction of the growth arrest genes gadd34, gadd45, and gadd153 by DNA-damaging agents. - Rat Genome Database

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Myc suppresses induction of the growth arrest genes gadd34, gadd45, and gadd153 by DNA-damaging agents.

Authors: Amundson, SA  Zhan, Q  Penn, LZ  Fornace AJ, JR 
Citation: Amundson SA, etal., Oncogene. 1998 Oct 29;17(17):2149-54.
RGD ID: 9999409
Pubmed: PMID:9811446   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.onc.1202136   (Journal Full-text)

The growth arrest and DNA damage inducible (gadd) genes are induced by various genotoxic and non-genotoxic stresses such as serum starvation, ultraviolet irradiation and treatment with alkylating agents. Their coordinate induction is a growth arrest signal which may play an important role in the response of cells to DNA damage. Conversely, c-myc is a strong proliferative signal, and overexpression of Myc is frequently observed in cancer cells. We have found that ectopic expression of v-myc in RAT-1 cells results in an attenuated induction of the three major gadd transcripts by methyl methanesulfonate (MMS), and almost completely blocks the response to ultraviolet (UV) radiation. Myc acts in part by reducing the stress-responsiveness of the gadd45 promoter, as a c-myc expression vector strongly suppressed activation of gadd45-reporter constructs. This activity of Myc localizes to a recently described GC-rich binding site within the gadd45 promoter. These results indicate that a coordinate down-regulation of the gadd gene response is one mechanism by which Myc can circumvent growth arrest and contribute to the neoplastic phenotype.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to methyl methanesulfonate  IEP 9999409 RGD 
cellular response to UV  IEP 9999409 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ppp1r15a  (protein phosphatase 1, regulatory subunit 15A)


Additional Information