A novel response element confers p63- and p73-specific activation of the WNT4 promoter

Motonobu Osada; Hannah Lui Park; Yuichi Nagakawa; Shahnaz Begum; Keishi Yamashita; Guojun Wu; Myoung Sook Kim; Barry Trink; David Sidransky

doi:10.1016/j.bbrc.2005.11.118

A novel response element confers p63- and p73-specific activation of the WNT4 promoter

Motonobu Osada, Hannah Lui Park, Yuichi Nagakawa, Shahnaz Begum, Keishi Yamashita, Guojun Wu, Myoung Sook Kim, Barry Trink, David Sidransky

School of Medicine

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

The p53 tumor suppressor gene family consists of three genes, p53, p63, and p73. p53 family proteins share high homology in their DNA-binding domains but exhibit diverse biological functions. In this study, we demonstrated differential target gene activation by specific p53, p63, and p73 induction in Saos2 cells by oligonucleotide microarray expression analysis. We further analyzed the WNT4 promoter, which was induced by p63 and p73 but not p53, in order to clarify the mechanism of differential target gene activation between the three family members. Luciferase analysis showed that the WNT4 promoter harbors two p63/p73 response elements, designated RE1 and RE2. RE1 resembles the canonical p53 response element (tandem repeats of RRRCWWGYYY), located between -141 and -121, while RE2 consists of a GC-rich sequence further downstream. Neither response element alone was able to confer transcriptional activity. It is thus likely that both RE1 and RE2 are necessary in rendering p63/p73-specific activation of the WNT4 promoter.

Original language	English (US)
Pages (from-to)	1120-1128
Number of pages	9
Journal	Biochemical and Biophysical Research Communications
Volume	339
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2005.11.118
State	Published - Jan 27 2006

Keywords

Microarray
Saos2
WNT4
p53
p53 response element
p63
p73

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.bbrc.2005.11.118

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title = "A novel response element confers p63- and p73-specific activation of the WNT4 promoter",

abstract = "The p53 tumor suppressor gene family consists of three genes, p53, p63, and p73. p53 family proteins share high homology in their DNA-binding domains but exhibit diverse biological functions. In this study, we demonstrated differential target gene activation by specific p53, p63, and p73 induction in Saos2 cells by oligonucleotide microarray expression analysis. We further analyzed the WNT4 promoter, which was induced by p63 and p73 but not p53, in order to clarify the mechanism of differential target gene activation between the three family members. Luciferase analysis showed that the WNT4 promoter harbors two p63/p73 response elements, designated RE1 and RE2. RE1 resembles the canonical p53 response element (tandem repeats of RRRCWWGYYY), located between -141 and -121, while RE2 consists of a GC-rich sequence further downstream. Neither response element alone was able to confer transcriptional activity. It is thus likely that both RE1 and RE2 are necessary in rendering p63/p73-specific activation of the WNT4 promoter.",

keywords = "Microarray, Saos2, WNT4, p53, p53 response element, p63, p73",

author = "Motonobu Osada and Park, {Hannah Lui} and Yuichi Nagakawa and Shahnaz Begum and Keishi Yamashita and Guojun Wu and Kim, {Myoung Sook} and Barry Trink and David Sidransky",

note = "Funding Information: This work was supported by NCI RO1 DE13561-03. pGL2-Basic WNT4-p1.2 was kindly provided by Dr. Melissa H. Little at the University of Queensland, Australia. The StAR −1300 reporter plasmid was a gift of Dr. L.K. Christenson at University of Pennsylvania, and the FGFR3 reporter p(−2311/−27)FR3-luc plasmids were kindly provided by Dr. David M. Ornitz at Washington University. ",

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AU - Osada, Motonobu

AU - Park, Hannah Lui

AU - Nagakawa, Yuichi

AU - Begum, Shahnaz

AU - Yamashita, Keishi

AU - Wu, Guojun

AU - Kim, Myoung Sook

AU - Trink, Barry

AU - Sidransky, David

N1 - Funding Information: This work was supported by NCI RO1 DE13561-03. pGL2-Basic WNT4-p1.2 was kindly provided by Dr. Melissa H. Little at the University of Queensland, Australia. The StAR −1300 reporter plasmid was a gift of Dr. L.K. Christenson at University of Pennsylvania, and the FGFR3 reporter p(−2311/−27)FR3-luc plasmids were kindly provided by Dr. David M. Ornitz at Washington University.

PY - 2006/1/27

Y1 - 2006/1/27

N2 - The p53 tumor suppressor gene family consists of three genes, p53, p63, and p73. p53 family proteins share high homology in their DNA-binding domains but exhibit diverse biological functions. In this study, we demonstrated differential target gene activation by specific p53, p63, and p73 induction in Saos2 cells by oligonucleotide microarray expression analysis. We further analyzed the WNT4 promoter, which was induced by p63 and p73 but not p53, in order to clarify the mechanism of differential target gene activation between the three family members. Luciferase analysis showed that the WNT4 promoter harbors two p63/p73 response elements, designated RE1 and RE2. RE1 resembles the canonical p53 response element (tandem repeats of RRRCWWGYYY), located between -141 and -121, while RE2 consists of a GC-rich sequence further downstream. Neither response element alone was able to confer transcriptional activity. It is thus likely that both RE1 and RE2 are necessary in rendering p63/p73-specific activation of the WNT4 promoter.

AB - The p53 tumor suppressor gene family consists of three genes, p53, p63, and p73. p53 family proteins share high homology in their DNA-binding domains but exhibit diverse biological functions. In this study, we demonstrated differential target gene activation by specific p53, p63, and p73 induction in Saos2 cells by oligonucleotide microarray expression analysis. We further analyzed the WNT4 promoter, which was induced by p63 and p73 but not p53, in order to clarify the mechanism of differential target gene activation between the three family members. Luciferase analysis showed that the WNT4 promoter harbors two p63/p73 response elements, designated RE1 and RE2. RE1 resembles the canonical p53 response element (tandem repeats of RRRCWWGYYY), located between -141 and -121, while RE2 consists of a GC-rich sequence further downstream. Neither response element alone was able to confer transcriptional activity. It is thus likely that both RE1 and RE2 are necessary in rendering p63/p73-specific activation of the WNT4 promoter.

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KW - WNT4

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KW - p53 response element

KW - p63

KW - p73

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A novel response element confers p63- and p73-specific activation of the WNT4 promoter

Abstract

Keywords

ASJC Scopus subject areas

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