The Drosophila homolog of the human tumor suppressor gene BHD interacts with the JAK-STAT and Dpp signaling pathways in regulating male germline stem cell maintenance
Birt–Hogg–Dubé syndrome (BHD) is a rare, inherited genodermatosis characterized by hair follicle hamartomas, kidney tumors and spontaneous pneumothorax. The BHD locus was mapped to chromosome 17p11.2 by linkage analysis, and germline mutations in a novel gene ( BHD ) were identified in a panel of BH...
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| Veröffentlicht in: | Oncogene 2006-09, Vol.25 (44), p.5933-5941 |
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| creator | Singh, S R Zhen, W Zheng, Z Wang, H Oh, S-W Liu, W Zbar, B Schmidt, L S Hou, S X |
| description | Birt–Hogg–Dubé syndrome (BHD) is a rare, inherited genodermatosis characterized by hair follicle hamartomas, kidney tumors and spontaneous pneumothorax. The
BHD
locus was mapped to chromosome 17p11.2 by linkage analysis, and germline mutations in a novel gene (
BHD
) were identified in a panel of BHD families. Using RNA interference to decrease expression of the
Drosophila
BHD homolog (
DBHD
), we have demonstrated that DBHD is required for male germline stem cell (GSC) maintenance in the fly testis. Reduction of
DBHD
gene activity suppresses the GSC overproliferation phenotype associated with overexpression of either
unpaired
(
upd
) or
decapentaplegic
(
dpp
). Further genetic interaction experiments suggest that DBHD regulates GSC maintenance downstream or in parallel of the JAK/STAT and Dpp signal-transduction pathways. These findings suggest that the BHD protein may regulate tumorigenesis through modulating stem cells in human. |
| doi_str_mv | 10.1038/sj.onc.1209593 |
| format | Article |
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BHD
locus was mapped to chromosome 17p11.2 by linkage analysis, and germline mutations in a novel gene (
BHD
) were identified in a panel of BHD families. Using RNA interference to decrease expression of the
Drosophila
BHD homolog (
DBHD
), we have demonstrated that DBHD is required for male germline stem cell (GSC) maintenance in the fly testis. Reduction of
DBHD
gene activity suppresses the GSC overproliferation phenotype associated with overexpression of either
unpaired
(
upd
) or
decapentaplegic
(
dpp
). Further genetic interaction experiments suggest that DBHD regulates GSC maintenance downstream or in parallel of the JAK/STAT and Dpp signal-transduction pathways. These findings suggest that the BHD protein may regulate tumorigenesis through modulating stem cells in human.</description><identifier>ISSN: 0950-9232</identifier><identifier>EISSN: 1476-5594</identifier><identifier>DOI: 10.1038/sj.onc.1209593</identifier><identifier>PMID: 16636660</identifier><identifier>CODEN: ONCNES</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Amino Acid Sequence ; Animals ; Apoptosis ; Biological and medical sciences ; Cell Biology ; Cell Differentiation - genetics ; Cell physiology ; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes ; Chromosome 17 ; Drosophila ; Drosophila - genetics ; Drosophila Proteins - genetics ; Drosophila Proteins - metabolism ; Drosophila Proteins - physiology ; Fundamental and applied biological sciences. Psychology ; Genetic disorders ; Genodermatosis ; Human Genetics ; Humans ; Insects ; Internal Medicine ; Janus Kinases ; Linkage analysis ; Male ; Medicine ; Medicine & Public Health ; Molecular and cellular biology ; Molecular Sequence Data ; Oncology ; original-article ; Phenotypes ; Pneumothorax ; Protein-Tyrosine Kinases - metabolism ; Proteins - physiology ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins - metabolism ; Proto-Oncogene Proteins - physiology ; RNA Interference ; RNA-mediated interference ; Signal transduction ; Signal Transduction - genetics ; Spermatozoa - cytology ; Spermatozoa - metabolism ; STAT Transcription Factors - metabolism ; Stem cells ; Stem Cells - cytology ; Stem Cells - metabolism ; Testis - cytology ; Testis - metabolism ; Transcription Factors - metabolism ; Tumor suppressor genes ; Tumor Suppressor Proteins - genetics ; Tumor Suppressor Proteins - metabolism ; Tumor Suppressor Proteins - physiology ; Tumorigenesis ; Tumors</subject><ispartof>Oncogene, 2006-09, Vol.25 (44), p.5933-5941</ispartof><rights>Springer Nature Limited 2006</rights><rights>2006 INIST-CNRS</rights><rights>COPYRIGHT 2006 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Sep 28, 2006</rights><rights>Nature Publishing Group 2006.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c587t-f8ad723ff28e283c5c09ae7087bde99c43e11d6e818b45ca6ca8239e6bb58e923</citedby><cites>FETCH-LOGICAL-c587t-f8ad723ff28e283c5c09ae7087bde99c43e11d6e818b45ca6ca8239e6bb58e923</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18155250$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16636660$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Singh, S R</creatorcontrib><creatorcontrib>Zhen, W</creatorcontrib><creatorcontrib>Zheng, Z</creatorcontrib><creatorcontrib>Wang, H</creatorcontrib><creatorcontrib>Oh, S-W</creatorcontrib><creatorcontrib>Liu, W</creatorcontrib><creatorcontrib>Zbar, B</creatorcontrib><creatorcontrib>Schmidt, L S</creatorcontrib><creatorcontrib>Hou, S X</creatorcontrib><title>The Drosophila homolog of the human tumor suppressor gene BHD interacts with the JAK-STAT and Dpp signaling pathways in regulating male germline stem cell maintenance</title><title>Oncogene</title><addtitle>Oncogene</addtitle><addtitle>Oncogene</addtitle><description>Birt–Hogg–Dubé syndrome (BHD) is a rare, inherited genodermatosis characterized by hair follicle hamartomas, kidney tumors and spontaneous pneumothorax. The
BHD
locus was mapped to chromosome 17p11.2 by linkage analysis, and germline mutations in a novel gene (
BHD
) were identified in a panel of BHD families. Using RNA interference to decrease expression of the
Drosophila
BHD homolog (
DBHD
), we have demonstrated that DBHD is required for male germline stem cell (GSC) maintenance in the fly testis. Reduction of
DBHD
gene activity suppresses the GSC overproliferation phenotype associated with overexpression of either
unpaired
(
upd
) or
decapentaplegic
(
dpp
). Further genetic interaction experiments suggest that DBHD regulates GSC maintenance downstream or in parallel of the JAK/STAT and Dpp signal-transduction pathways. These findings suggest that the BHD protein may regulate tumorigenesis through modulating stem cells in human.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>Cell Biology</subject><subject>Cell Differentiation - genetics</subject><subject>Cell physiology</subject><subject>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</subject><subject>Chromosome 17</subject><subject>Drosophila</subject><subject>Drosophila - genetics</subject><subject>Drosophila Proteins - genetics</subject><subject>Drosophila Proteins - metabolism</subject><subject>Drosophila Proteins - physiology</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetic disorders</subject><subject>Genodermatosis</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Insects</subject><subject>Internal Medicine</subject><subject>Janus Kinases</subject><subject>Linkage analysis</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Molecular and cellular biology</subject><subject>Molecular Sequence Data</subject><subject>Oncology</subject><subject>original-article</subject><subject>Phenotypes</subject><subject>Pneumothorax</subject><subject>Protein-Tyrosine Kinases - metabolism</subject><subject>Proteins - physiology</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Proto-Oncogene Proteins - physiology</subject><subject>RNA Interference</subject><subject>RNA-mediated interference</subject><subject>Signal transduction</subject><subject>Signal Transduction - genetics</subject><subject>Spermatozoa - cytology</subject><subject>Spermatozoa - metabolism</subject><subject>STAT Transcription Factors - metabolism</subject><subject>Stem cells</subject><subject>Stem Cells - cytology</subject><subject>Stem Cells - metabolism</subject><subject>Testis - cytology</subject><subject>Testis - metabolism</subject><subject>Transcription Factors - metabolism</subject><subject>Tumor suppressor genes</subject><subject>Tumor Suppressor Proteins - genetics</subject><subject>Tumor Suppressor Proteins - metabolism</subject><subject>Tumor Suppressor Proteins - physiology</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><issn>0950-9232</issn><issn>1476-5594</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkk1v1DAQhiMEokvhyhFZILhl64_4I8elCxSoxIHlHHmdyccqsUOcqOof4ncyoSuthFpVPtgaP_POePwmyWtG14wKcxEP6-DdmnGay1w8SVYs0yqVMs-eJiuM0TTngp8lL2I8UEp1Tvnz5IwpJZRSdJX82TVAtmOIYWjazpIm9KELNQkVmfCmmXvryTT3YSRxHoYRYsRjDR7Ix6staf0Eo3VTJDft1PxL-bb5nv7cbXbE-pJsh4HEtva2a31NBjs1N_Y2YhoZoZ47Oy3h3naAkmOPEJA4QU8cdB3GF3lvvYOXybPKdhFeHffz5NfnT7vLq_T6x5evl5vr1Emjp7QyttRcVBU3wI1w0tHcgqZG70vIc5cJYKxUYJjZZ9JZ5azhIge130sDOKnz5MOd7jCG3zPEqejbuDRjPYQ5FsrgAKWmj4KcCaa1Eo-CLNeZ5Joh-O4_8BDmESeHYipjQnNmNFJvH6S4FiIXVJykapxs0foqTPhJS91iw_AFMpNqKbi-h8JVQt-64KFqMX5fgkO_xBGqYhjb3o63BaPF4sYiHgp0Y3F0Iya8OTY773soT_jRfgi8PwI2OttVI_51G0-cYVJyuXAXd1zEK49WOb36gdJ_Abb092c</recordid><startdate>20060928</startdate><enddate>20060928</enddate><creator>Singh, S R</creator><creator>Zhen, W</creator><creator>Zheng, Z</creator><creator>Wang, H</creator><creator>Oh, S-W</creator><creator>Liu, W</creator><creator>Zbar, B</creator><creator>Schmidt, L S</creator><creator>Hou, S X</creator><general>Nature Publishing Group UK</general><general>Nature Publishing</general><general>Nature Publishing Group</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7SS</scope><scope>7X8</scope></search><sort><creationdate>20060928</creationdate><title>The Drosophila homolog of the human tumor suppressor gene BHD interacts with the JAK-STAT and Dpp signaling pathways in regulating male germline stem cell maintenance</title><author>Singh, S R ; Zhen, W ; Zheng, Z ; Wang, H ; Oh, S-W ; Liu, W ; Zbar, B ; Schmidt, L S ; Hou, S X</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c587t-f8ad723ff28e283c5c09ae7087bde99c43e11d6e818b45ca6ca8239e6bb58e923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>Cell Biology</topic><topic>Cell Differentiation - genetics</topic><topic>Cell physiology</topic><topic>Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes</topic><topic>Chromosome 17</topic><topic>Drosophila</topic><topic>Drosophila - genetics</topic><topic>Drosophila Proteins - genetics</topic><topic>Drosophila Proteins - metabolism</topic><topic>Drosophila Proteins - physiology</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genetic disorders</topic><topic>Genodermatosis</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Insects</topic><topic>Internal Medicine</topic><topic>Janus Kinases</topic><topic>Linkage analysis</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Molecular and cellular biology</topic><topic>Molecular Sequence Data</topic><topic>Oncology</topic><topic>original-article</topic><topic>Phenotypes</topic><topic>Pneumothorax</topic><topic>Protein-Tyrosine Kinases - metabolism</topic><topic>Proteins - physiology</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Proto-Oncogene Proteins - physiology</topic><topic>RNA Interference</topic><topic>RNA-mediated interference</topic><topic>Signal transduction</topic><topic>Signal Transduction - genetics</topic><topic>Spermatozoa - cytology</topic><topic>Spermatozoa - metabolism</topic><topic>STAT Transcription Factors - metabolism</topic><topic>Stem cells</topic><topic>Stem Cells - cytology</topic><topic>Stem Cells - metabolism</topic><topic>Testis - cytology</topic><topic>Testis - metabolism</topic><topic>Transcription Factors - metabolism</topic><topic>Tumor suppressor genes</topic><topic>Tumor Suppressor Proteins - genetics</topic><topic>Tumor Suppressor Proteins - metabolism</topic><topic>Tumor Suppressor Proteins - physiology</topic><topic>Tumorigenesis</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Singh, S R</creatorcontrib><creatorcontrib>Zhen, W</creatorcontrib><creatorcontrib>Zheng, Z</creatorcontrib><creatorcontrib>Wang, H</creatorcontrib><creatorcontrib>Oh, S-W</creatorcontrib><creatorcontrib>Liu, W</creatorcontrib><creatorcontrib>Zbar, B</creatorcontrib><creatorcontrib>Schmidt, L S</creatorcontrib><creatorcontrib>Hou, S X</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>MEDLINE - Academic</collection><jtitle>Oncogene</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Singh, S R</au><au>Zhen, W</au><au>Zheng, Z</au><au>Wang, H</au><au>Oh, S-W</au><au>Liu, W</au><au>Zbar, B</au><au>Schmidt, L S</au><au>Hou, S X</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Drosophila homolog of the human tumor suppressor gene BHD interacts with the JAK-STAT and Dpp signaling pathways in regulating male germline stem cell maintenance</atitle><jtitle>Oncogene</jtitle><stitle>Oncogene</stitle><addtitle>Oncogene</addtitle><date>2006-09-28</date><risdate>2006</risdate><volume>25</volume><issue>44</issue><spage>5933</spage><epage>5941</epage><pages>5933-5941</pages><issn>0950-9232</issn><eissn>1476-5594</eissn><coden>ONCNES</coden><abstract>Birt–Hogg–Dubé syndrome (BHD) is a rare, inherited genodermatosis characterized by hair follicle hamartomas, kidney tumors and spontaneous pneumothorax. The
BHD
locus was mapped to chromosome 17p11.2 by linkage analysis, and germline mutations in a novel gene (
BHD
) were identified in a panel of BHD families. Using RNA interference to decrease expression of the
Drosophila
BHD homolog (
DBHD
), we have demonstrated that DBHD is required for male germline stem cell (GSC) maintenance in the fly testis. Reduction of
DBHD
gene activity suppresses the GSC overproliferation phenotype associated with overexpression of either
unpaired
(
upd
) or
decapentaplegic
(
dpp
). Further genetic interaction experiments suggest that DBHD regulates GSC maintenance downstream or in parallel of the JAK/STAT and Dpp signal-transduction pathways. These findings suggest that the BHD protein may regulate tumorigenesis through modulating stem cells in human.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>16636660</pmid><doi>10.1038/sj.onc.1209593</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| issn | 0950-9232 1476-5594 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68902570 |
| source | MEDLINE; Nature Journals Online; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Amino Acid Sequence Animals Apoptosis Biological and medical sciences Cell Biology Cell Differentiation - genetics Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Chromosome 17 Drosophila Drosophila - genetics Drosophila Proteins - genetics Drosophila Proteins - metabolism Drosophila Proteins - physiology Fundamental and applied biological sciences. Psychology Genetic disorders Genodermatosis Human Genetics Humans Insects Internal Medicine Janus Kinases Linkage analysis Male Medicine Medicine & Public Health Molecular and cellular biology Molecular Sequence Data Oncology original-article Phenotypes Pneumothorax Protein-Tyrosine Kinases - metabolism Proteins - physiology Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins - physiology RNA Interference RNA-mediated interference Signal transduction Signal Transduction - genetics Spermatozoa - cytology Spermatozoa - metabolism STAT Transcription Factors - metabolism Stem cells Stem Cells - cytology Stem Cells - metabolism Testis - cytology Testis - metabolism Transcription Factors - metabolism Tumor suppressor genes Tumor Suppressor Proteins - genetics Tumor Suppressor Proteins - metabolism Tumor Suppressor Proteins - physiology Tumorigenesis Tumors |
| title | The Drosophila homolog of the human tumor suppressor gene BHD interacts with the JAK-STAT and Dpp signaling pathways in regulating male germline stem cell maintenance |
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