Heterogeneity of transcriptional activity of mutant p53 proteins and p53 DNA target sequences

Jeou Yuan Chen, Walter D. Funk, Woodring E. Wright, Jerry W. Shay, John D. Minna

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

Transcriptional activity of p53 was monitored by cotransfection of pCMV expression vectors containing wild-type and mutant p53 cDNAs into the p53-null H1299 lung cancer cells along with luciferase reporter plasmids containing different p53 target sequences in the 5′ regulatory region: fragment A of the ribosomal gene cluster (RGC); p53 consensus sequence (p53CON); or a tandemly linked RGC+p53CON sequence. Our results show: (1) wild-type p53 stimulates the transcription of reporter genes with p53CON and RGC in their 5′ region while most p53 mutants occurring in human cancers have lost this activity; (2) the R273H mutant retains transcriptional activity for the p53CON sequence but not RGC; (3) some mutants are temperature-sensitive for the transcriptional activity with the p53CON but not the RGC sequence; (4) p53 mutants vary in their ability to inhibit wild-type p53 transactivation but there is no difference between p53CON and RGC sequences; (5) lung cancer cells with endogenous mutant p53 proteins (M246I in H23 cells and R248L in H322 cells) retain transcriptional activity for the p53CON but not the RGC sequence. We conclude that p53 DNA target sequences vary in their response to mutant p53 proteins, and that p53 mutants vary in several transactivation related functions.

Original languageEnglish (US)
Pages (from-to)2159-2166
Number of pages8
JournalOncogene
Volume8
Issue number8
StatePublished - Aug 1993

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Consensus Sequence
Mutant Proteins
Multigene Family
Transcriptional Activation
Lung Neoplasms
Nucleic Acid Regulatory Sequences
Luciferases
Reporter Genes
Plasmids
Complementary DNA
Temperature
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this

Heterogeneity of transcriptional activity of mutant p53 proteins and p53 DNA target sequences. / Chen, Jeou Yuan; Funk, Walter D.; Wright, Woodring E.; Shay, Jerry W.; Minna, John D.

In: Oncogene, Vol. 8, No. 8, 08.1993, p. 2159-2166.

Research output: Contribution to journalArticle

Chen, Jeou Yuan ; Funk, Walter D. ; Wright, Woodring E. ; Shay, Jerry W. ; Minna, John D. / Heterogeneity of transcriptional activity of mutant p53 proteins and p53 DNA target sequences. In: Oncogene. 1993 ; Vol. 8, No. 8. pp. 2159-2166.
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