A PTCH1 Homolog Transcriptionally Activated by p53 Suppresses Hedgehog Signaling

被引：29

作者：

Chung, Jon H. ^{[1
]}

Larsen, Andrew R. ^{[1
]}

Chen, Evan ^{[1
]}

Bunz, Fred ^{[1
]}

机构：

[1] Kimmel Canc Ctr Johns Hopkins, Dept Radiat Oncol & Mol Radiat Sci, Baltimore, MD 21231 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2014年 / 289卷 / 47期

基金：

美国国家卫生研究院;

关键词：

TUMOR SUPPRESSION; DRUG-SENSITIVITY; CANCER-CELLS; HUMAN GENOME; MEDULLOBLASTOMA; GENE; TUMORIGENESIS; ENCYCLOPEDIA; PATTERNS; SUGGESTS;

D O I：

10.1074/jbc.M114.597203

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The p53-mediated responses to DNA damage and the Hedgehog (Hh) signaling pathway are each recurrently dysregulated in many types of human cancer. Here we describe PTCH53, a p53 target gene that is homologous to the tumor suppressor gene PTCH1 and can function as a repressor of Hh pathway activation. PTCH53 (previously designated PTCHD4) was highly responsive to p53 in vitro and was among a small number of genes that were consistently expressed at reduced levels in diverse TP53 mutant cell lines and human tumors. Increased expression of PTCH53 inhibited canonical Hh signaling by the G protein-coupled receptor SMO. PTCH53 thus delineates a novel, inducible pathway by which p53 can repress tumorigenic Hh signals.

引用

页码：33020 / 33031

页数：12

共 35 条

[1] Learning from Jekyll to control Hyde: Hedgehog signaling in development and cancer [J].

Barakat, Monique T. ;

Humke, Eric W. ;

Scott, Matthew P. .

TRENDS IN MOLECULAR MEDICINE, 2010, 16 (08) :337-348

[2] The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity [J].

Barretina, Jordi ;

Caponigro, Giordano ;

Stransky, Nicolas ;

Venkatesan, Kavitha ;

Margolin, Adam A. ;

Kim, Sungjoon ;

Wilson, Christopher J. ;

Lehar, Joseph ;

Kryukov, Gregory V. ;

Sonkin, Dmitriy ;

Reddy, Anupama ;

Liu, Manway ;

Murray, Lauren ;

Berger, Michael F. ;

Monahan, John E. ;

Morais, Paula ;

Meltzer, Jodi ;

Korejwa, Adam ;

Jane-Valbuena, Judit ;

Mapa, Felipa A. ;

Thibault, Joseph ;

Bric-Furlong, Eva ;

Raman, Pichai ;

Shipway, Aaron ;

Engels, Ingo H. ;

Cheng, Jill ;

Yu, Guoying K. ;

Yu, Jianjun ;

Aspesi, Peter, Jr. ;

de Silva, Melanie ;

Jagtap, Kalpana ;

Jones, Michael D. ;

Wang, Li ;

Hatton, Charles ;

Palescandolo, Emanuele ;

Gupta, Supriya ;

Mahan, Scott ;

Sougnez, Carrie ;

Onofrio, Robert C. ;

Liefeld, Ted ;

MacConaill, Laura ;

Winckler, Wendy ;

Reich, Michael ;

Li, Nanxin ;

Mesirov, Jill P. ;

Gabriel, Stacey B. ;

Getz, Gad ;

Ardlie, Kristin ;

Chan, Vivien ;

Myer, Vic E. .

NATURE, 2012, 483 (7391) :603-607

[3] Deconstructing p53 transcriptional networks in tumor suppression [J].

Bieging, Kathryn T. ;

Attardi, Laura D. .

TRENDS IN CELL BIOLOGY, 2012, 22 (02) :97-106

[4] Distinct p53 genomic binding patterns in normal and cancer-derived human cells [J].

Botcheva, Krassimira ;

McCorkle, Sean R. ;

McCombie, W. R. ;

Dunn, John J. ;

Anderson, Carl W. .

CELL CYCLE, 2011, 10 (24) :4237-4249

[5] A loss-of-function mutation in PTCH1 suggests a role for autocrine hedgehog signaling in colorectal tumorigenesis [J].

Chung, Jon H. ;

Bunz, Fred .

ONCOTARGET, 2013, 4 (12) :2208-2211

[6] An integrated encyclopedia of DNA elements in the human genome [J].

Dunham, Ian ;

Kundaje, Anshul ;

Aldred, Shelley F. ;

Collins, Patrick J. ;

Davis, CarrieA. ;

Doyle, Francis ;

Epstein, Charles B. ;

Frietze, Seth ;

Harrow, Jennifer ;

Kaul, Rajinder ;

Khatun, Jainab ;

Lajoie, Bryan R. ;

Landt, Stephen G. ;

Lee, Bum-Kyu ;

Pauli, Florencia ;

Rosenbloom, Kate R. ;

Sabo, Peter ;

Safi, Alexias ;

Sanyal, Amartya ;

Shoresh, Noam ;

Simon, Jeremy M. ;

Song, Lingyun ;

Trinklein, Nathan D. ;

Altshuler, Robert C. ;

Birney, Ewan ;

Brown, James B. ;

Cheng, Chao ;

Djebali, Sarah ;

Dong, Xianjun ;

Dunham, Ian ;

Ernst, Jason ;

Furey, Terrence S. ;

Gerstein, Mark ;

Giardine, Belinda ;

Greven, Melissa ;

Hardison, Ross C. ;

Harris, Robert S. ;

Herrero, Javier ;

Hoffman, Michael M. ;

Iyer, Sowmya ;

Kellis, Manolis ;

Khatun, Jainab ;

Kheradpour, Pouya ;

Kundaje, Anshul ;

Lassmann, Timo ;

Li, Qunhua ;

Lin, Xinying ;

Marinov, Georgi K. ;

Merkel, Angelika ;

Mortazavi, Ali .

NATURE, 2012, 489 (7414) :57-74

[7] DEFINITION OF A CONSENSUS BINDING-SITE FOR P53 [J].

ELDEIRY, WS ;

KERN, SE ;

PIETENPOL, JA ;

KINZLER, KW ;

VOGELSTEIN, B .

NATURE GENETICS, 1992, 1 (01) :45-49

[8] WAF1, A POTENTIAL MEDIATOR OF P53 TUMOR SUPPRESSION [J].

ELDEIRY, WS ;

TOKINO, T ;

VELCULESCU, VE ;

LEVY, DB ;

PARSONS, R ;

TRENT, JM ;

LIN, D ;

MERCER, WE ;

KINZLER, KW ;

VOGELSTEIN, B .

CELL, 1993, 75 (04) :817-825

[9] Integrative Analysis of Complex Cancer Genomics and Clinical Profiles Using the cBioPortal [J].

Gao, Jianjiong ;

Aksoy, Buelent Arman ;

Dogrusoz, Ugur ;

Dresdner, Gideon ;

Gross, Benjamin ;

Sumer, S. Onur ;

Sun, Yichao ;

Jacobsen, Anders ;

Sinha, Rileen ;

Larsson, Erik ;

Cerami, Ethan ;

Sander, Chris ;

Schultz, Nikolaus .

SCIENCE SIGNALING, 2013, 6 (269) :pl1

[10] Systematic identification of genomic markers of drug sensitivity in cancer cells [J].

Garnett, Mathew J. ;

Edelman, Elena J. ;

Heidorn, Sonja J. ;

Greenman, Chris D. ;

Dastur, Anahita ;

Lau, King Wai ;

Greninger, Patricia ;

Thompson, I. Richard ;

Luo, Xi ;

Soares, Jorge ;

Liu, Qingsong ;

Iorio, Francesco ;

Surdez, Didier ;

Chen, Li ;

Milano, Randy J. ;

Bignell, Graham R. ;

Tam, Ah T. ;

Davies, Helen ;

Stevenson, Jesse A. ;

Barthorpe, Syd ;

Lutz, Stephen R. ;

Kogera, Fiona ;

Lawrence, Karl ;

McLaren-Douglas, Anne ;

Mitropoulos, Xeni ;

Mironenko, Tatiana ;

Thi, Helen ;

Richardson, Laura ;

Zhou, Wenjun ;

Jewitt, Frances ;

Zhang, Tinghu ;

O'Brien, Patrick ;

Boisvert, Jessica L. ;

Price, Stacey ;

Hur, Wooyoung ;

Yang, Wanjuan ;

Deng, Xianming ;

Butler, Adam ;

Choi, Hwan Geun ;

Chang, JaeWon ;

Baselga, Jose ;

Stamenkovic, Ivan ;

Engelman, Jeffrey A. ;

Sharma, Sreenath V. ;

Delattre, Olivier ;

Saez-Rodriguez, Julio ;

Gray, Nathanael S. ;

Settleman, Jeffrey ;

Futreal, P. Andrew ;

Haber, Daniel A. .

NATURE, 2012, 483 (7391) :570-U87

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