p63 and p73 Transactivate Differentiation Gene Promoters in Human Keratinocytes
p53 and its two homologues, p73 and p63, share considerable structural similarities, an ability to interact between themselves and to transactivate the same promoters, including for example p21. Furthermore, p73 can induce cell death via its interaction with c-Abl. In contrast, p63 has been demonstr...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2000-06, Vol.273 (1), p.342-346 |
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| creator | De Laurenzi, Vincenzo Rossi, Antonello Terrinoni, Alessandro Barcaroli, Daniela Levrero, Massimo Costanzo, Antonio Knight, Richard A. Guerrieri, Piero Melino, Gerry |
| description | p53 and its two homologues, p73 and p63, share considerable structural similarities, an ability to interact between themselves and to transactivate the same promoters, including for example p21. Furthermore, p73 can induce cell death via its interaction with c-Abl. In contrast, p63 has been demonstrated to be essential for limb and skin formation. We evaluated the expression of p63 and p73 in differentiating human keratinocytes in vitro. Skin biopsy and primary cultures of normal human epidermal keratinocytes (NHEK) express both p73 and p63. NHEK induced to differentiate in vitro by high calcium exposure show induction of p73 δ and downregulation of all isoforms of p63. This latter gene is predominantly expressed in its transcriptionally inactive form, ΔNp63. We further evaluated the effect of either p73s or p63 transfected in either NHEK or transformed human keratinocytes (HaCat cells). p73 γ, δ, and p63 were able to transactivate the promoters of loricrin and involucrin in both NHEK and HaCat cells. These results suggest the involvement of both p73 and p63 genes in keratinocyte terminal differentiation. |
| doi_str_mv | 10.1006/bbrc.2000.2932 |
| format | Article |
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Furthermore, p73 can induce cell death via its interaction with c-Abl. In contrast, p63 has been demonstrated to be essential for limb and skin formation. We evaluated the expression of p63 and p73 in differentiating human keratinocytes in vitro. Skin biopsy and primary cultures of normal human epidermal keratinocytes (NHEK) express both p73 and p63. NHEK induced to differentiate in vitro by high calcium exposure show induction of p73 δ and downregulation of all isoforms of p63. This latter gene is predominantly expressed in its transcriptionally inactive form, ΔNp63. We further evaluated the effect of either p73s or p63 transfected in either NHEK or transformed human keratinocytes (HaCat cells). p73 γ, δ, and p63 were able to transactivate the promoters of loricrin and involucrin in both NHEK and HaCat cells. These results suggest the involvement of both p73 and p63 genes in keratinocyte terminal differentiation.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1006/bbrc.2000.2932</identifier><identifier>PMID: 10873608</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>apoptosis ; Calcium - pharmacology ; Cell Differentiation - drug effects ; Cell Differentiation - genetics ; Cell Line, Transformed ; Cells, Cultured ; differentiation ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Down-Regulation - drug effects ; Genes, Reporter - genetics ; Genes, Tumor Suppressor ; Humans ; keratinocytes ; Keratinocytes - cytology ; Keratinocytes - drug effects ; Keratinocytes - metabolism ; Membrane Proteins - genetics ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; p53 ; p63 ; p73 ; Phosphoproteins - genetics ; Phosphoproteins - metabolism ; Promoter Regions, Genetic - genetics ; Protein Isoforms - genetics ; Protein Isoforms - metabolism ; Protein Precursors - genetics ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; skin ; Trans-Activators ; Transcription Factors ; Transcriptional Activation - genetics ; Transfection ; Tumor Protein p73 ; Tumor Suppressor Proteins</subject><ispartof>Biochemical and biophysical research communications, 2000-06, Vol.273 (1), p.342-346</ispartof><rights>2000 Academic Press</rights><rights>Copyright 2000 Academic Press.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c406t-50d0d0c7122e1ec37ae1391ca7592446f1f16ced82c3f60673f223ffa634030c3</citedby><cites>FETCH-LOGICAL-c406t-50d0d0c7122e1ec37ae1391ca7592446f1f16ced82c3f60673f223ffa634030c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1006/bbrc.2000.2932$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10873608$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>De Laurenzi, Vincenzo</creatorcontrib><creatorcontrib>Rossi, Antonello</creatorcontrib><creatorcontrib>Terrinoni, Alessandro</creatorcontrib><creatorcontrib>Barcaroli, Daniela</creatorcontrib><creatorcontrib>Levrero, Massimo</creatorcontrib><creatorcontrib>Costanzo, Antonio</creatorcontrib><creatorcontrib>Knight, Richard A.</creatorcontrib><creatorcontrib>Guerrieri, Piero</creatorcontrib><creatorcontrib>Melino, Gerry</creatorcontrib><title>p63 and p73 Transactivate Differentiation Gene Promoters in Human Keratinocytes</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>p53 and its two homologues, p73 and p63, share considerable structural similarities, an ability to interact between themselves and to transactivate the same promoters, including for example p21. Furthermore, p73 can induce cell death via its interaction with c-Abl. In contrast, p63 has been demonstrated to be essential for limb and skin formation. We evaluated the expression of p63 and p73 in differentiating human keratinocytes in vitro. Skin biopsy and primary cultures of normal human epidermal keratinocytes (NHEK) express both p73 and p63. NHEK induced to differentiate in vitro by high calcium exposure show induction of p73 δ and downregulation of all isoforms of p63. This latter gene is predominantly expressed in its transcriptionally inactive form, ΔNp63. We further evaluated the effect of either p73s or p63 transfected in either NHEK or transformed human keratinocytes (HaCat cells). p73 γ, δ, and p63 were able to transactivate the promoters of loricrin and involucrin in both NHEK and HaCat cells. These results suggest the involvement of both p73 and p63 genes in keratinocyte terminal differentiation.</description><subject>apoptosis</subject><subject>Calcium - pharmacology</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Line, Transformed</subject><subject>Cells, Cultured</subject><subject>differentiation</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Down-Regulation - drug effects</subject><subject>Genes, Reporter - genetics</subject><subject>Genes, Tumor Suppressor</subject><subject>Humans</subject><subject>keratinocytes</subject><subject>Keratinocytes - cytology</subject><subject>Keratinocytes - drug effects</subject><subject>Keratinocytes - metabolism</subject><subject>Membrane Proteins - genetics</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>p53</subject><subject>p63</subject><subject>p73</subject><subject>Phosphoproteins - genetics</subject><subject>Phosphoproteins - metabolism</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Protein Isoforms - genetics</subject><subject>Protein Isoforms - metabolism</subject><subject>Protein Precursors - genetics</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>skin</subject><subject>Trans-Activators</subject><subject>Transcription Factors</subject><subject>Transcriptional Activation - genetics</subject><subject>Transfection</subject><subject>Tumor Protein p73</subject><subject>Tumor Suppressor Proteins</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kE1LAzEQhoMotn5cPUpO3rbOJGu2e5SqrVioBwVvIc1OINLN1iQV_Pfu0h68yBwGhmdeZh7GrhAmCKBu1-toJwIAJqKW4oiNEWooBEJ5zMb9WBWixo8RO0vpEwCxVPUpGyFMK6lgOmarrZLchIZvK8nfognJ2Oy_TSb-4J2jSCF7k30X-JwC8dfYtV2mmLgPfLFrTeAvFHsgdPYnU7pgJ85sEl0e-jl7f3p8my2K5Wr-PLtfFrYElYs7aPqyFQpBSFZWhlDWaE11V4uyVA4dKkvNVFjpFKhKOiGkc0bJEiRYec5u9rnb2H3tKGXd-mRpszGBul3SQ7JErHtwsgdt7FKK5PQ2-tbEH42gB4V6UKgHhXpQ2C9cH5J365aaP_jeWQ9M9wD1_317ijpZT6G_1keyWTed_y_7F63nftw</recordid><startdate>20000624</startdate><enddate>20000624</enddate><creator>De Laurenzi, Vincenzo</creator><creator>Rossi, Antonello</creator><creator>Terrinoni, Alessandro</creator><creator>Barcaroli, Daniela</creator><creator>Levrero, Massimo</creator><creator>Costanzo, Antonio</creator><creator>Knight, Richard A.</creator><creator>Guerrieri, Piero</creator><creator>Melino, Gerry</creator><general>Elsevier Inc</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>7X8</scope></search><sort><creationdate>20000624</creationdate><title>p63 and p73 Transactivate Differentiation Gene Promoters in Human Keratinocytes</title><author>De Laurenzi, Vincenzo ; Rossi, Antonello ; Terrinoni, Alessandro ; Barcaroli, Daniela ; Levrero, Massimo ; Costanzo, Antonio ; Knight, Richard A. ; Guerrieri, Piero ; Melino, Gerry</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c406t-50d0d0c7122e1ec37ae1391ca7592446f1f16ced82c3f60673f223ffa634030c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>apoptosis</topic><topic>Calcium - pharmacology</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Line, Transformed</topic><topic>Cells, Cultured</topic><topic>differentiation</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Down-Regulation - drug effects</topic><topic>Genes, Reporter - genetics</topic><topic>Genes, Tumor Suppressor</topic><topic>Humans</topic><topic>keratinocytes</topic><topic>Keratinocytes - cytology</topic><topic>Keratinocytes - drug effects</topic><topic>Keratinocytes - metabolism</topic><topic>Membrane Proteins - genetics</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>p53</topic><topic>p63</topic><topic>p73</topic><topic>Phosphoproteins - genetics</topic><topic>Phosphoproteins - metabolism</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Protein Isoforms - genetics</topic><topic>Protein Isoforms - metabolism</topic><topic>Protein Precursors - genetics</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>skin</topic><topic>Trans-Activators</topic><topic>Transcription Factors</topic><topic>Transcriptional Activation - genetics</topic><topic>Transfection</topic><topic>Tumor Protein p73</topic><topic>Tumor Suppressor Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>De Laurenzi, Vincenzo</creatorcontrib><creatorcontrib>Rossi, Antonello</creatorcontrib><creatorcontrib>Terrinoni, Alessandro</creatorcontrib><creatorcontrib>Barcaroli, Daniela</creatorcontrib><creatorcontrib>Levrero, Massimo</creatorcontrib><creatorcontrib>Costanzo, Antonio</creatorcontrib><creatorcontrib>Knight, Richard A.</creatorcontrib><creatorcontrib>Guerrieri, Piero</creatorcontrib><creatorcontrib>Melino, Gerry</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>De Laurenzi, Vincenzo</au><au>Rossi, Antonello</au><au>Terrinoni, Alessandro</au><au>Barcaroli, Daniela</au><au>Levrero, Massimo</au><au>Costanzo, Antonio</au><au>Knight, Richard A.</au><au>Guerrieri, Piero</au><au>Melino, Gerry</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>p63 and p73 Transactivate Differentiation Gene Promoters in Human Keratinocytes</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2000-06-24</date><risdate>2000</risdate><volume>273</volume><issue>1</issue><spage>342</spage><epage>346</epage><pages>342-346</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>p53 and its two homologues, p73 and p63, share considerable structural similarities, an ability to interact between themselves and to transactivate the same promoters, including for example p21. Furthermore, p73 can induce cell death via its interaction with c-Abl. In contrast, p63 has been demonstrated to be essential for limb and skin formation. We evaluated the expression of p63 and p73 in differentiating human keratinocytes in vitro. Skin biopsy and primary cultures of normal human epidermal keratinocytes (NHEK) express both p73 and p63. NHEK induced to differentiate in vitro by high calcium exposure show induction of p73 δ and downregulation of all isoforms of p63. This latter gene is predominantly expressed in its transcriptionally inactive form, ΔNp63. We further evaluated the effect of either p73s or p63 transfected in either NHEK or transformed human keratinocytes (HaCat cells). p73 γ, δ, and p63 were able to transactivate the promoters of loricrin and involucrin in both NHEK and HaCat cells. These results suggest the involvement of both p73 and p63 genes in keratinocyte terminal differentiation.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>10873608</pmid><doi>10.1006/bbrc.2000.2932</doi><tpages>5</tpages></addata></record> |
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| subjects | apoptosis Calcium - pharmacology Cell Differentiation - drug effects Cell Differentiation - genetics Cell Line, Transformed Cells, Cultured differentiation DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Down-Regulation - drug effects Genes, Reporter - genetics Genes, Tumor Suppressor Humans keratinocytes Keratinocytes - cytology Keratinocytes - drug effects Keratinocytes - metabolism Membrane Proteins - genetics Nuclear Proteins - genetics Nuclear Proteins - metabolism p53 p63 p73 Phosphoproteins - genetics Phosphoproteins - metabolism Promoter Regions, Genetic - genetics Protein Isoforms - genetics Protein Isoforms - metabolism Protein Precursors - genetics RNA, Messenger - genetics RNA, Messenger - metabolism skin Trans-Activators Transcription Factors Transcriptional Activation - genetics Transfection Tumor Protein p73 Tumor Suppressor Proteins |
| title | p63 and p73 Transactivate Differentiation Gene Promoters in Human Keratinocytes |
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