ΔNp63α and TAp63α regulate transcription of genes with distinct biological functions in cancer and development

Guojun Wu, Shuji Nomoto, Mohammad Obaidul Hoque, Tatiana Dracheva, Motonabu Osada, Chyi Chia Richard Lee, Seung Myung Dong, Zhongmin Guo, Nicole Benoit, Yoram Cohen, Peggy Rechthand, Joseph Califano, Chul So Moon, Edward Ratovitski, Jin Jen, David Sidransky, Barry Trink

Research output: Contribution to journalArticle

194 Citations (Scopus)

Abstract

The p63 gene shows remarkable structural similarity to the p53 and p73 genes. Because of two promoters, the p63 gene generates two types of protein isoforms, TAp63 and ΔNp63. Each type yields three isotypes (α, β, γ) because of differential splicing of the p63 COOH terminus. The purpose of this study was to determine whether there is a functional link between the distinct p63 isotypes in their transcriptional regulation of downstream targets and their role in various cellular functions. TAp63α and ΔNp63α adenovirus expression vectors were introduced into Saos2 cells for 4 and 24 h, and then gene profiling was performed using a DNA microarray chip analysis. Seventy-four genes (> 2-fold change in expression) were identified that overlapped between two independent studies. Thirty-five genes were selected for direct expression testing of which 27 were confirmed by reverse transcription-PCR or Northern blot analysis. A survey of these genes shows that p63 can regulate a wide range of downstream gene targets with various cellular functions, including cell cycle control, stress, and signal transduction. Our study thus revealed p63 transcriptional regulation of many genes in cancer and development while often demonstrating opposing regulatory functions for TAp63α and ΔNp63α.

Original languageEnglish (US)
Pages (from-to)2351-2357
Number of pages7
JournalCancer Research
Volume63
Issue number10
StatePublished - May 15 2003
Externally publishedYes

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Genes
Neoplasms
Oligonucleotide Array Sequence Analysis
Neoplasm Genes
p53 Genes
Microarray Analysis
Cell Cycle Checkpoints
Adenoviridae
Northern Blotting
Reverse Transcription
Signal Transduction
Protein Isoforms
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Wu, G., Nomoto, S., Hoque, M. O., Dracheva, T., Osada, M., Lee, C. C. R., ... Trink, B. (2003). ΔNp63α and TAp63α regulate transcription of genes with distinct biological functions in cancer and development. Cancer Research, 63(10), 2351-2357.

ΔNp63α and TAp63α regulate transcription of genes with distinct biological functions in cancer and development. / Wu, Guojun; Nomoto, Shuji; Hoque, Mohammad Obaidul; Dracheva, Tatiana; Osada, Motonabu; Lee, Chyi Chia Richard; Dong, Seung Myung; Guo, Zhongmin; Benoit, Nicole; Cohen, Yoram; Rechthand, Peggy; Califano, Joseph; Moon, Chul So; Ratovitski, Edward; Jen, Jin; Sidransky, David; Trink, Barry.

In: Cancer Research, Vol. 63, No. 10, 15.05.2003, p. 2351-2357.

Research output: Contribution to journalArticle

Wu, G, Nomoto, S, Hoque, MO, Dracheva, T, Osada, M, Lee, CCR, Dong, SM, Guo, Z, Benoit, N, Cohen, Y, Rechthand, P, Califano, J, Moon, CS, Ratovitski, E, Jen, J, Sidransky, D & Trink, B 2003, 'ΔNp63α and TAp63α regulate transcription of genes with distinct biological functions in cancer and development', Cancer Research, vol. 63, no. 10, pp. 2351-2357.
Wu G, Nomoto S, Hoque MO, Dracheva T, Osada M, Lee CCR et al. ΔNp63α and TAp63α regulate transcription of genes with distinct biological functions in cancer and development. Cancer Research. 2003 May 15;63(10):2351-2357.
Wu, Guojun ; Nomoto, Shuji ; Hoque, Mohammad Obaidul ; Dracheva, Tatiana ; Osada, Motonabu ; Lee, Chyi Chia Richard ; Dong, Seung Myung ; Guo, Zhongmin ; Benoit, Nicole ; Cohen, Yoram ; Rechthand, Peggy ; Califano, Joseph ; Moon, Chul So ; Ratovitski, Edward ; Jen, Jin ; Sidransky, David ; Trink, Barry. / ΔNp63α and TAp63α regulate transcription of genes with distinct biological functions in cancer and development. In: Cancer Research. 2003 ; Vol. 63, No. 10. pp. 2351-2357.
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abstract = "The p63 gene shows remarkable structural similarity to the p53 and p73 genes. Because of two promoters, the p63 gene generates two types of protein isoforms, TAp63 and ΔNp63. Each type yields three isotypes (α, β, γ) because of differential splicing of the p63 COOH terminus. The purpose of this study was to determine whether there is a functional link between the distinct p63 isotypes in their transcriptional regulation of downstream targets and their role in various cellular functions. TAp63α and ΔNp63α adenovirus expression vectors were introduced into Saos2 cells for 4 and 24 h, and then gene profiling was performed using a DNA microarray chip analysis. Seventy-four genes (> 2-fold change in expression) were identified that overlapped between two independent studies. Thirty-five genes were selected for direct expression testing of which 27 were confirmed by reverse transcription-PCR or Northern blot analysis. A survey of these genes shows that p63 can regulate a wide range of downstream gene targets with various cellular functions, including cell cycle control, stress, and signal transduction. Our study thus revealed p63 transcriptional regulation of many genes in cancer and development while often demonstrating opposing regulatory functions for TAp63α and ΔNp63α.",
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AU - Osada, Motonabu

AU - Lee, Chyi Chia Richard

AU - Dong, Seung Myung

AU - Guo, Zhongmin

AU - Benoit, Nicole

AU - Cohen, Yoram

AU - Rechthand, Peggy

AU - Califano, Joseph

AU - Moon, Chul So

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AU - Jen, Jin

AU - Sidransky, David

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