A dominant negative form of p63 inhibits apoptosis in a p53-independent manner

Hae ock Lee; Jung Hwa Lee; Eunhee Choi; Ja Young Seol; Yungdae Yun; Hyunsook Lee

doi:10.1016/j.bbrc.2006.03.128

A dominant negative form of p63 inhibits apoptosis in a p53-independent manner

Hae ock Lee
, Jung Hwa Lee
, Eunhee Choi
, Ja Young Seol
, Yungdae Yun
, Hyunsook Lee

Department of Microbiology

Seoul National University
Ewha Womans University

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

31 Scopus citations

Abstract

Stem cells are a source of differentiated cells in multiple tissues. If genetic alterations occur in stem cells, the problem persists and malignant cancers may arise. ΔNp63α-a homologue of the tumor suppressor p53-is exclusively expressed in proliferating undifferentiated epithelial cells and cancer cells of epidermal origin. Here, we show that ΔNp63α antagonizes DNA damage-induced apoptosis in a p53-independent manner. We found that upon cellular injury, ΔNp63α must be downregulated before apoptotic program can be activated. The 5637 cell line has abundant levels of ΔNp63α and mutant p53, and it is resistant to DNA damage-induced apoptosis. The knockdown of ΔNp63α by RNA interference sensitized these cells to apoptosis upon genotoxic insult. This suggests that ΔNp63α plays an anti-apoptotic role regardless of the p53 status. Considering the frequent mutations of p53 in tumor cells, our results provide important implications for the treatment of cancers in which p63 is amplified.

Original language	English
Pages (from-to)	166-172
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	344
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2006.03.128
State	Published - 26 May 2006

Bibliographical note

Funding Information:
We are grateful to Dr. David Kimelman (University of Washington, Seattle) for critically reading the manuscript. We also thank Dr. William Hahn (Dana Farber Institute, Boston) for kindly providing us with human mammary epithelial cells. This work was supported by a fund from the Korea Research Foundation (R01-2003-000-10396-0) and National Cancer Center (3344-20050066).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Apoptosis
DNA damage
Tumorigenesis
p53
ΔNp63α

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10.1016/j.bbrc.2006.03.128

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title = "A dominant negative form of p63 inhibits apoptosis in a p53-independent manner",

abstract = "Stem cells are a source of differentiated cells in multiple tissues. If genetic alterations occur in stem cells, the problem persists and malignant cancers may arise. ΔNp63α-a homologue of the tumor suppressor p53-is exclusively expressed in proliferating undifferentiated epithelial cells and cancer cells of epidermal origin. Here, we show that ΔNp63α antagonizes DNA damage-induced apoptosis in a p53-independent manner. We found that upon cellular injury, ΔNp63α must be downregulated before apoptotic program can be activated. The 5637 cell line has abundant levels of ΔNp63α and mutant p53, and it is resistant to DNA damage-induced apoptosis. The knockdown of ΔNp63α by RNA interference sensitized these cells to apoptosis upon genotoxic insult. This suggests that ΔNp63α plays an anti-apoptotic role regardless of the p53 status. Considering the frequent mutations of p53 in tumor cells, our results provide important implications for the treatment of cancers in which p63 is amplified.",

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author = "Lee, \{Hae ock\} and Lee, \{Jung Hwa\} and Eunhee Choi and Seol, \{Ja Young\} and Yungdae Yun and Hyunsook Lee",

note = "Funding Information: We are grateful to Dr. David Kimelman (University of Washington, Seattle) for critically reading the manuscript. We also thank Dr. William Hahn (Dana Farber Institute, Boston) for kindly providing us with human mammary epithelial cells. This work was supported by a fund from the Korea Research Foundation (R01-2003-000-10396-0) and National Cancer Center (3344-20050066).",

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AU - Lee, Hae ock

AU - Lee, Jung Hwa

AU - Choi, Eunhee

AU - Seol, Ja Young

AU - Yun, Yungdae

AU - Lee, Hyunsook

N1 - Funding Information: We are grateful to Dr. David Kimelman (University of Washington, Seattle) for critically reading the manuscript. We also thank Dr. William Hahn (Dana Farber Institute, Boston) for kindly providing us with human mammary epithelial cells. This work was supported by a fund from the Korea Research Foundation (R01-2003-000-10396-0) and National Cancer Center (3344-20050066).

PY - 2006/5/26

Y1 - 2006/5/26

N2 - Stem cells are a source of differentiated cells in multiple tissues. If genetic alterations occur in stem cells, the problem persists and malignant cancers may arise. ΔNp63α-a homologue of the tumor suppressor p53-is exclusively expressed in proliferating undifferentiated epithelial cells and cancer cells of epidermal origin. Here, we show that ΔNp63α antagonizes DNA damage-induced apoptosis in a p53-independent manner. We found that upon cellular injury, ΔNp63α must be downregulated before apoptotic program can be activated. The 5637 cell line has abundant levels of ΔNp63α and mutant p53, and it is resistant to DNA damage-induced apoptosis. The knockdown of ΔNp63α by RNA interference sensitized these cells to apoptosis upon genotoxic insult. This suggests that ΔNp63α plays an anti-apoptotic role regardless of the p53 status. Considering the frequent mutations of p53 in tumor cells, our results provide important implications for the treatment of cancers in which p63 is amplified.

AB - Stem cells are a source of differentiated cells in multiple tissues. If genetic alterations occur in stem cells, the problem persists and malignant cancers may arise. ΔNp63α-a homologue of the tumor suppressor p53-is exclusively expressed in proliferating undifferentiated epithelial cells and cancer cells of epidermal origin. Here, we show that ΔNp63α antagonizes DNA damage-induced apoptosis in a p53-independent manner. We found that upon cellular injury, ΔNp63α must be downregulated before apoptotic program can be activated. The 5637 cell line has abundant levels of ΔNp63α and mutant p53, and it is resistant to DNA damage-induced apoptosis. The knockdown of ΔNp63α by RNA interference sensitized these cells to apoptosis upon genotoxic insult. This suggests that ΔNp63α plays an anti-apoptotic role regardless of the p53 status. Considering the frequent mutations of p53 in tumor cells, our results provide important implications for the treatment of cancers in which p63 is amplified.

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KW - DNA damage

KW - Tumorigenesis

KW - p53

KW - ΔNp63α

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IS - 1

ER -

A dominant negative form of p63 inhibits apoptosis in a p53-independent manner

Abstract

Bibliographical note

UN SDGs

Keywords

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