The Short Stature Homeodomain Protein SHOX Induces Cellular Growth Arrest and Apoptosis and Is Expressed in Human Growth Plate Chondrocytes
Mutations in the homeobox gene SHOX cause growth retardation and the skeletal abnormalities associated with Léri-Weill, Langer, and Turner syndromes. Little is known about the mechanism underlying these SHOX -related inherited disorders of bone formation. Here we demonstrate that SHOX expression in...
Gespeichert in:
| Veröffentlicht in: | The Journal of biological chemistry 2004-08, Vol.279 (35), p.37103-37114 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 37114 |
|---|---|
| container_issue | 35 |
| container_start_page | 37103 |
| container_title | The Journal of biological chemistry |
| container_volume | 279 |
| creator | Marchini, Antonio Marttila, Tiina Winter, Anja Caldeira, Sandra Malanchi, Ilaria Blaschke, Rüdiger J. Häcker, Beate Rao, Ercole Karperien, Marcel Wit, Jan M. Richter, Wiltrud Tommasino, Massimo Rappold, Gudrun A. |
| description | Mutations in the homeobox gene SHOX cause growth retardation and the skeletal abnormalities associated with Léri-Weill, Langer, and Turner syndromes. Little
is known about the mechanism underlying these SHOX -related inherited disorders of bone formation. Here we demonstrate that SHOX expression in osteogenic stable cell lines,
primary oral fibroblasts, and primary chondrocytes leads to cell cycle arrest and apoptosis. These events are associated with
alterations in the expression of several cellular genes, including pRB, p53 , and the cyclin kinase inhibitors p21 Cip1 and p27 Kip1 . A SHOX mutant, such as seen in Léri-Weill syndrome patients, does not display these activities of the wild type protein.
We have also shown that endogenous SHOX is mainly expressed in hypertrophic/apoptotic chondrocytes of the growth plate, strongly
suggesting that the protein plays a direct role in regulating the differentiation of these cells. This study provides the
first insight into the biological function of SHOX as regulator of cellular proliferation and viability and relates these
cellular events to the phenotypic consequences of SHOX deficiency. |
| doi_str_mv | 10.1074/jbc.M307006200 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_18033764</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>18033764</sourcerecordid><originalsourceid>FETCH-LOGICAL-c457t-8c30e7191e2b69a3b3cc165f7362c0bb52ff0c503777ef9b97e910a32d2c88953</originalsourceid><addsrcrecordid>eNpFkMFu1DAQhi0EokvhyhH5gLhlGcdxHB9Xq9JdqaiVtki9WY4zIamSONiO2j4DL43pbtW5jEbzzT8zPyGfGawZyOL7fW3XPzlIgDIHeENWDCqeccHu3pIVQM4ylYvqjHwI4R5SFIq9J2dMsEKoQqzI39sO6aFzPtJDNHHxSHduRNe40fQTvfEuYsqH3fUd3U_NYjHQLQ7DMhhPL717iB3deI8hUjM1dDO7ObrQh-dqH-jF45yaARuaVHbLaKaXqZvBRKTbzk2Nd_YpYvhI3rVmCPjplM_Jrx8Xt9tddnV9ud9urjJbCBmzynJAyRTDvC6V4TW3lpWilbzMLdS1yNsWrAAupcRW1UqiYmB43uS2qpTg5-TbUXf27s-STtdjH2x6ykzolqBZBZzLskjg-gha70Lw2OrZ96PxT5qB_m-_TvbrV_vTwJeT8lKP2LziJ78T8PUIdP3v7qH3qOve2Q5HnUuludBcsrT8H30OjX4</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>18033764</pqid></control><display><type>article</type><title>The Short Stature Homeodomain Protein SHOX Induces Cellular Growth Arrest and Apoptosis and Is Expressed in Human Growth Plate Chondrocytes</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Marchini, Antonio ; Marttila, Tiina ; Winter, Anja ; Caldeira, Sandra ; Malanchi, Ilaria ; Blaschke, Rüdiger J. ; Häcker, Beate ; Rao, Ercole ; Karperien, Marcel ; Wit, Jan M. ; Richter, Wiltrud ; Tommasino, Massimo ; Rappold, Gudrun A.</creator><creatorcontrib>Marchini, Antonio ; Marttila, Tiina ; Winter, Anja ; Caldeira, Sandra ; Malanchi, Ilaria ; Blaschke, Rüdiger J. ; Häcker, Beate ; Rao, Ercole ; Karperien, Marcel ; Wit, Jan M. ; Richter, Wiltrud ; Tommasino, Massimo ; Rappold, Gudrun A.</creatorcontrib><description>Mutations in the homeobox gene SHOX cause growth retardation and the skeletal abnormalities associated with Léri-Weill, Langer, and Turner syndromes. Little
is known about the mechanism underlying these SHOX -related inherited disorders of bone formation. Here we demonstrate that SHOX expression in osteogenic stable cell lines,
primary oral fibroblasts, and primary chondrocytes leads to cell cycle arrest and apoptosis. These events are associated with
alterations in the expression of several cellular genes, including pRB, p53 , and the cyclin kinase inhibitors p21 Cip1 and p27 Kip1 . A SHOX mutant, such as seen in Léri-Weill syndrome patients, does not display these activities of the wild type protein.
We have also shown that endogenous SHOX is mainly expressed in hypertrophic/apoptotic chondrocytes of the growth plate, strongly
suggesting that the protein plays a direct role in regulating the differentiation of these cells. This study provides the
first insight into the biological function of SHOX as regulator of cellular proliferation and viability and relates these
cellular events to the phenotypic consequences of SHOX deficiency.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M307006200</identifier><identifier>PMID: 15145945</identifier><language>eng</language><publisher>United States: American Society for Biochemistry and Molecular Biology</publisher><subject>Antimetabolites, Antineoplastic - pharmacology ; Apoptosis ; Blotting, Western ; Body Height ; Bromodeoxyuridine - pharmacology ; Cell Cycle ; Cell Cycle Proteins - metabolism ; Cell Division ; Cell Line, Tumor ; Cell Separation ; Cells, Cultured ; Chondrocytes - metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclin-Dependent Kinase Inhibitor p27 ; Cyclins - metabolism ; Fibroblasts - metabolism ; Flow Cytometry ; Gene Deletion ; Growth Plate - metabolism ; Homeodomain Proteins - chemistry ; Homeodomain Proteins - genetics ; Homeodomain Proteins - physiology ; Humans ; Immunohistochemistry ; In Situ Nick-End Labeling ; Mouth - metabolism ; Mutation ; Protein Structure, Tertiary ; Retinoblastoma Protein - metabolism ; Retroviridae - genetics ; Short Stature Homeobox Protein ; Time Factors ; Transcription Factors - genetics ; Transcription Factors - physiology ; Tumor Suppressor Protein p53 - metabolism ; Tumor Suppressor Proteins - metabolism</subject><ispartof>The Journal of biological chemistry, 2004-08, Vol.279 (35), p.37103-37114</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c457t-8c30e7191e2b69a3b3cc165f7362c0bb52ff0c503777ef9b97e910a32d2c88953</citedby><cites>FETCH-LOGICAL-c457t-8c30e7191e2b69a3b3cc165f7362c0bb52ff0c503777ef9b97e910a32d2c88953</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15145945$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Marchini, Antonio</creatorcontrib><creatorcontrib>Marttila, Tiina</creatorcontrib><creatorcontrib>Winter, Anja</creatorcontrib><creatorcontrib>Caldeira, Sandra</creatorcontrib><creatorcontrib>Malanchi, Ilaria</creatorcontrib><creatorcontrib>Blaschke, Rüdiger J.</creatorcontrib><creatorcontrib>Häcker, Beate</creatorcontrib><creatorcontrib>Rao, Ercole</creatorcontrib><creatorcontrib>Karperien, Marcel</creatorcontrib><creatorcontrib>Wit, Jan M.</creatorcontrib><creatorcontrib>Richter, Wiltrud</creatorcontrib><creatorcontrib>Tommasino, Massimo</creatorcontrib><creatorcontrib>Rappold, Gudrun A.</creatorcontrib><title>The Short Stature Homeodomain Protein SHOX Induces Cellular Growth Arrest and Apoptosis and Is Expressed in Human Growth Plate Chondrocytes</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Mutations in the homeobox gene SHOX cause growth retardation and the skeletal abnormalities associated with Léri-Weill, Langer, and Turner syndromes. Little
is known about the mechanism underlying these SHOX -related inherited disorders of bone formation. Here we demonstrate that SHOX expression in osteogenic stable cell lines,
primary oral fibroblasts, and primary chondrocytes leads to cell cycle arrest and apoptosis. These events are associated with
alterations in the expression of several cellular genes, including pRB, p53 , and the cyclin kinase inhibitors p21 Cip1 and p27 Kip1 . A SHOX mutant, such as seen in Léri-Weill syndrome patients, does not display these activities of the wild type protein.
We have also shown that endogenous SHOX is mainly expressed in hypertrophic/apoptotic chondrocytes of the growth plate, strongly
suggesting that the protein plays a direct role in regulating the differentiation of these cells. This study provides the
first insight into the biological function of SHOX as regulator of cellular proliferation and viability and relates these
cellular events to the phenotypic consequences of SHOX deficiency.</description><subject>Antimetabolites, Antineoplastic - pharmacology</subject><subject>Apoptosis</subject><subject>Blotting, Western</subject><subject>Body Height</subject><subject>Bromodeoxyuridine - pharmacology</subject><subject>Cell Cycle</subject><subject>Cell Cycle Proteins - metabolism</subject><subject>Cell Division</subject><subject>Cell Line, Tumor</subject><subject>Cell Separation</subject><subject>Cells, Cultured</subject><subject>Chondrocytes - metabolism</subject><subject>Cyclin-Dependent Kinase Inhibitor p21</subject><subject>Cyclin-Dependent Kinase Inhibitor p27</subject><subject>Cyclins - metabolism</subject><subject>Fibroblasts - metabolism</subject><subject>Flow Cytometry</subject><subject>Gene Deletion</subject><subject>Growth Plate - metabolism</subject><subject>Homeodomain Proteins - chemistry</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - physiology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>In Situ Nick-End Labeling</subject><subject>Mouth - metabolism</subject><subject>Mutation</subject><subject>Protein Structure, Tertiary</subject><subject>Retinoblastoma Protein - metabolism</subject><subject>Retroviridae - genetics</subject><subject>Short Stature Homeobox Protein</subject><subject>Time Factors</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - physiology</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Tumor Suppressor Proteins - metabolism</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkMFu1DAQhi0EokvhyhH5gLhlGcdxHB9Xq9JdqaiVtki9WY4zIamSONiO2j4DL43pbtW5jEbzzT8zPyGfGawZyOL7fW3XPzlIgDIHeENWDCqeccHu3pIVQM4ylYvqjHwI4R5SFIq9J2dMsEKoQqzI39sO6aFzPtJDNHHxSHduRNe40fQTvfEuYsqH3fUd3U_NYjHQLQ7DMhhPL717iB3deI8hUjM1dDO7ObrQh-dqH-jF45yaARuaVHbLaKaXqZvBRKTbzk2Nd_YpYvhI3rVmCPjplM_Jrx8Xt9tddnV9ud9urjJbCBmzynJAyRTDvC6V4TW3lpWilbzMLdS1yNsWrAAupcRW1UqiYmB43uS2qpTg5-TbUXf27s-STtdjH2x6ykzolqBZBZzLskjg-gha70Lw2OrZ96PxT5qB_m-_TvbrV_vTwJeT8lKP2LziJ78T8PUIdP3v7qH3qOve2Q5HnUuludBcsrT8H30OjX4</recordid><startdate>20040827</startdate><enddate>20040827</enddate><creator>Marchini, Antonio</creator><creator>Marttila, Tiina</creator><creator>Winter, Anja</creator><creator>Caldeira, Sandra</creator><creator>Malanchi, Ilaria</creator><creator>Blaschke, Rüdiger J.</creator><creator>Häcker, Beate</creator><creator>Rao, Ercole</creator><creator>Karperien, Marcel</creator><creator>Wit, Jan M.</creator><creator>Richter, Wiltrud</creator><creator>Tommasino, Massimo</creator><creator>Rappold, Gudrun A.</creator><general>American Society for Biochemistry and Molecular Biology</general><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>7QP</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>20040827</creationdate><title>The Short Stature Homeodomain Protein SHOX Induces Cellular Growth Arrest and Apoptosis and Is Expressed in Human Growth Plate Chondrocytes</title><author>Marchini, Antonio ; Marttila, Tiina ; Winter, Anja ; Caldeira, Sandra ; Malanchi, Ilaria ; Blaschke, Rüdiger J. ; Häcker, Beate ; Rao, Ercole ; Karperien, Marcel ; Wit, Jan M. ; Richter, Wiltrud ; Tommasino, Massimo ; Rappold, Gudrun A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c457t-8c30e7191e2b69a3b3cc165f7362c0bb52ff0c503777ef9b97e910a32d2c88953</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Antimetabolites, Antineoplastic - pharmacology</topic><topic>Apoptosis</topic><topic>Blotting, Western</topic><topic>Body Height</topic><topic>Bromodeoxyuridine - pharmacology</topic><topic>Cell Cycle</topic><topic>Cell Cycle Proteins - metabolism</topic><topic>Cell Division</topic><topic>Cell Line, Tumor</topic><topic>Cell Separation</topic><topic>Cells, Cultured</topic><topic>Chondrocytes - metabolism</topic><topic>Cyclin-Dependent Kinase Inhibitor p21</topic><topic>Cyclin-Dependent Kinase Inhibitor p27</topic><topic>Cyclins - metabolism</topic><topic>Fibroblasts - metabolism</topic><topic>Flow Cytometry</topic><topic>Gene Deletion</topic><topic>Growth Plate - metabolism</topic><topic>Homeodomain Proteins - chemistry</topic><topic>Homeodomain Proteins - genetics</topic><topic>Homeodomain Proteins - physiology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>In Situ Nick-End Labeling</topic><topic>Mouth - metabolism</topic><topic>Mutation</topic><topic>Protein Structure, Tertiary</topic><topic>Retinoblastoma Protein - metabolism</topic><topic>Retroviridae - genetics</topic><topic>Short Stature Homeobox Protein</topic><topic>Time Factors</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - physiology</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Tumor Suppressor Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Marchini, Antonio</creatorcontrib><creatorcontrib>Marttila, Tiina</creatorcontrib><creatorcontrib>Winter, Anja</creatorcontrib><creatorcontrib>Caldeira, Sandra</creatorcontrib><creatorcontrib>Malanchi, Ilaria</creatorcontrib><creatorcontrib>Blaschke, Rüdiger J.</creatorcontrib><creatorcontrib>Häcker, Beate</creatorcontrib><creatorcontrib>Rao, Ercole</creatorcontrib><creatorcontrib>Karperien, Marcel</creatorcontrib><creatorcontrib>Wit, Jan M.</creatorcontrib><creatorcontrib>Richter, Wiltrud</creatorcontrib><creatorcontrib>Tommasino, Massimo</creatorcontrib><creatorcontrib>Rappold, Gudrun A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Marchini, Antonio</au><au>Marttila, Tiina</au><au>Winter, Anja</au><au>Caldeira, Sandra</au><au>Malanchi, Ilaria</au><au>Blaschke, Rüdiger J.</au><au>Häcker, Beate</au><au>Rao, Ercole</au><au>Karperien, Marcel</au><au>Wit, Jan M.</au><au>Richter, Wiltrud</au><au>Tommasino, Massimo</au><au>Rappold, Gudrun A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Short Stature Homeodomain Protein SHOX Induces Cellular Growth Arrest and Apoptosis and Is Expressed in Human Growth Plate Chondrocytes</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2004-08-27</date><risdate>2004</risdate><volume>279</volume><issue>35</issue><spage>37103</spage><epage>37114</epage><pages>37103-37114</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Mutations in the homeobox gene SHOX cause growth retardation and the skeletal abnormalities associated with Léri-Weill, Langer, and Turner syndromes. Little
is known about the mechanism underlying these SHOX -related inherited disorders of bone formation. Here we demonstrate that SHOX expression in osteogenic stable cell lines,
primary oral fibroblasts, and primary chondrocytes leads to cell cycle arrest and apoptosis. These events are associated with
alterations in the expression of several cellular genes, including pRB, p53 , and the cyclin kinase inhibitors p21 Cip1 and p27 Kip1 . A SHOX mutant, such as seen in Léri-Weill syndrome patients, does not display these activities of the wild type protein.
We have also shown that endogenous SHOX is mainly expressed in hypertrophic/apoptotic chondrocytes of the growth plate, strongly
suggesting that the protein plays a direct role in regulating the differentiation of these cells. This study provides the
first insight into the biological function of SHOX as regulator of cellular proliferation and viability and relates these
cellular events to the phenotypic consequences of SHOX deficiency.</abstract><cop>United States</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>15145945</pmid><doi>10.1074/jbc.M307006200</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9258 |
| ispartof | The Journal of biological chemistry, 2004-08, Vol.279 (35), p.37103-37114 |
| issn | 0021-9258 1083-351X |
| language | eng |
| recordid | cdi_proquest_miscellaneous_18033764 |
| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Antimetabolites, Antineoplastic - pharmacology Apoptosis Blotting, Western Body Height Bromodeoxyuridine - pharmacology Cell Cycle Cell Cycle Proteins - metabolism Cell Division Cell Line, Tumor Cell Separation Cells, Cultured Chondrocytes - metabolism Cyclin-Dependent Kinase Inhibitor p21 Cyclin-Dependent Kinase Inhibitor p27 Cyclins - metabolism Fibroblasts - metabolism Flow Cytometry Gene Deletion Growth Plate - metabolism Homeodomain Proteins - chemistry Homeodomain Proteins - genetics Homeodomain Proteins - physiology Humans Immunohistochemistry In Situ Nick-End Labeling Mouth - metabolism Mutation Protein Structure, Tertiary Retinoblastoma Protein - metabolism Retroviridae - genetics Short Stature Homeobox Protein Time Factors Transcription Factors - genetics Transcription Factors - physiology Tumor Suppressor Protein p53 - metabolism Tumor Suppressor Proteins - metabolism |
| title | The Short Stature Homeodomain Protein SHOX Induces Cellular Growth Arrest and Apoptosis and Is Expressed in Human Growth Plate Chondrocytes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-26T14%3A36%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20Short%20Stature%20Homeodomain%20Protein%20SHOX%20Induces%20Cellular%20Growth%20Arrest%20and%20Apoptosis%20and%20Is%20Expressed%20in%20Human%20Growth%20Plate%20Chondrocytes&rft.jtitle=The%20Journal%20of%20biological%20chemistry&rft.au=Marchini,%20Antonio&rft.date=2004-08-27&rft.volume=279&rft.issue=35&rft.spage=37103&rft.epage=37114&rft.pages=37103-37114&rft.issn=0021-9258&rft.eissn=1083-351X&rft_id=info:doi/10.1074/jbc.M307006200&rft_dat=%3Cproquest_cross%3E18033764%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=18033764&rft_id=info:pmid/15145945&rfr_iscdi=true |