Cell cycle-dependent phosphorylation of the translational repressor eIF-4E binding protein-1 (4E-BP1)
A fundamental control point in the regulation of the initiation of protein synthesis is the formation of the eukaryotic initiation factor 4F (eIF-4F) complex. The formation of this complex depends upon the availability of the mRNA cap binding protein, eIF-4E, which is sequestered away from the trans...
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| Veröffentlicht in: | Current biology 2001-09, Vol.11 (17), p.1374-1379 |
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| creator | Heesom, Kate J. Gampel, Alexandra Mellor, Harry Denton, Richard M. |
| description | A fundamental control point in the regulation of the initiation of protein synthesis is the formation of the eukaryotic initiation factor 4F (eIF-4F) complex. The formation of this complex depends upon the availability of the mRNA cap binding protein, eIF-4E, which is sequestered away from the translational machinery by the tight association of eIF-4E binding proteins (4E-BPs). Phosphorylation of 4E-BP1 is critical in causing its dissociation from eIF-4E, leaving 4E available to form translationally active eIF-4F complexes, switching on mRNA translation. In this report, we provide the first evidence that the phosphorylation of 4E-BP1 increases during mitosis and identify Ser-65 and Thr-70 as phosphorylated sites. Phosphorylation of Thr-70 has been implicated in the regulation of 4E-BP1 function, but the kinase phosphorylating this site was unknown. We show that the cyclin-dependent kinase, cdc2, phosphorylates 4E-BP1 at Thr-70 and that phosphorylation of this site is permissive for Ser-65 phosphorylation. Crucially, the increased phosphorylation of 4E-BP1 during mitosis results in its complete dissociation from eIF-4E. |
| doi_str_mv | 10.1016/S0960-9822(01)00422-5 |
| format | Article |
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The formation of this complex depends upon the availability of the mRNA cap binding protein, eIF-4E, which is sequestered away from the translational machinery by the tight association of eIF-4E binding proteins (4E-BPs). Phosphorylation of 4E-BP1 is critical in causing its dissociation from eIF-4E, leaving 4E available to form translationally active eIF-4F complexes, switching on mRNA translation. In this report, we provide the first evidence that the phosphorylation of 4E-BP1 increases during mitosis and identify Ser-65 and Thr-70 as phosphorylated sites. Phosphorylation of Thr-70 has been implicated in the regulation of 4E-BP1 function, but the kinase phosphorylating this site was unknown. We show that the cyclin-dependent kinase, cdc2, phosphorylates 4E-BP1 at Thr-70 and that phosphorylation of this site is permissive for Ser-65 phosphorylation. Crucially, the increased phosphorylation of 4E-BP1 during mitosis results in its complete dissociation from eIF-4E.</description><identifier>ISSN: 0960-9822</identifier><identifier>EISSN: 1879-0445</identifier><identifier>DOI: 10.1016/S0960-9822(01)00422-5</identifier><identifier>PMID: 11553333</identifier><language>eng</language><publisher>England: Elsevier Inc</publisher><subject>4E-BP1 protein ; Adaptor Proteins, Signal Transducing ; Carrier Proteins - metabolism ; Cdc2 protein ; CDC2 Protein Kinase - metabolism ; Cell Cycle ; eIF-4E binding protein 1 ; Eukaryotic Initiation Factor-4E ; HeLa Cells ; Humans ; initiation factor eIF-4E ; Peptide Initiation Factors - metabolism ; Phosphoproteins - metabolism ; Phosphorylation ; Protein Biosynthesis ; Repressor Proteins - metabolism</subject><ispartof>Current biology, 2001-09, Vol.11 (17), p.1374-1379</ispartof><rights>2001 Elsevier Science Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c371t-2792669c78299a8c34ef63962097a1cde3ea48780b71d4a4e2dbb23dc571b1023</citedby><cites>FETCH-LOGICAL-c371t-2792669c78299a8c34ef63962097a1cde3ea48780b71d4a4e2dbb23dc571b1023</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960982201004225$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11553333$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Heesom, Kate J.</creatorcontrib><creatorcontrib>Gampel, Alexandra</creatorcontrib><creatorcontrib>Mellor, Harry</creatorcontrib><creatorcontrib>Denton, Richard M.</creatorcontrib><title>Cell cycle-dependent phosphorylation of the translational repressor eIF-4E binding protein-1 (4E-BP1)</title><title>Current biology</title><addtitle>Curr Biol</addtitle><description>A fundamental control point in the regulation of the initiation of protein synthesis is the formation of the eukaryotic initiation factor 4F (eIF-4F) complex. The formation of this complex depends upon the availability of the mRNA cap binding protein, eIF-4E, which is sequestered away from the translational machinery by the tight association of eIF-4E binding proteins (4E-BPs). Phosphorylation of 4E-BP1 is critical in causing its dissociation from eIF-4E, leaving 4E available to form translationally active eIF-4F complexes, switching on mRNA translation. In this report, we provide the first evidence that the phosphorylation of 4E-BP1 increases during mitosis and identify Ser-65 and Thr-70 as phosphorylated sites. Phosphorylation of Thr-70 has been implicated in the regulation of 4E-BP1 function, but the kinase phosphorylating this site was unknown. We show that the cyclin-dependent kinase, cdc2, phosphorylates 4E-BP1 at Thr-70 and that phosphorylation of this site is permissive for Ser-65 phosphorylation. Crucially, the increased phosphorylation of 4E-BP1 during mitosis results in its complete dissociation from eIF-4E.</description><subject>4E-BP1 protein</subject><subject>Adaptor Proteins, Signal Transducing</subject><subject>Carrier Proteins - metabolism</subject><subject>Cdc2 protein</subject><subject>CDC2 Protein Kinase - metabolism</subject><subject>Cell Cycle</subject><subject>eIF-4E binding protein 1</subject><subject>Eukaryotic Initiation Factor-4E</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>initiation factor eIF-4E</subject><subject>Peptide Initiation Factors - metabolism</subject><subject>Phosphoproteins - metabolism</subject><subject>Phosphorylation</subject><subject>Protein Biosynthesis</subject><subject>Repressor Proteins - metabolism</subject><issn>0960-9822</issn><issn>1879-0445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9rGzEQxUVJaJy0H6FFpxAflGgk7Wp1Kqlx_kAghbZnoZXGjcpau5XWBX_7rGOTHCMQguE380bvEfIF-CVwqK9-clNzZhohLjjMOVdCsOoDmUGjDeNKVUdk9oqckNNS_nIOojH1R3ICUFVyOjOCC-w66re-QxZwwBQwjXR46st087ZzY-wT7Vd0fEI6ZpfKvuQ6mnHIWEqfKd7fMLWkbUwhpj90yP2IMTGgF2rJvv-A-SdyvHJdwc-H94z8vln-Wtyxh8fb-8X1A_NSw8iENqKujdeNMMY1Xipc1dLUghvtwAeU6FSjG95qCMopFKFthQy-0tACF_KMnO_nTiv822AZ7ToWP_3QJew3xWqAepqt3wWhAQApqwms9qDPfSkZV3bIce3y1gK3uyDsSxB257LlYF-CsLu-rweBTbvG8NZ1cH4Cvu0BnPz4HzHb4iMmjyFm9KMNfXxH4hksJ5ZS</recordid><startdate>20010904</startdate><enddate>20010904</enddate><creator>Heesom, Kate J.</creator><creator>Gampel, Alexandra</creator><creator>Mellor, Harry</creator><creator>Denton, Richard M.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</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>7TM</scope><scope>7X8</scope></search><sort><creationdate>20010904</creationdate><title>Cell cycle-dependent phosphorylation of the translational repressor eIF-4E binding protein-1 (4E-BP1)</title><author>Heesom, Kate J. ; Gampel, Alexandra ; Mellor, Harry ; Denton, Richard M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c371t-2792669c78299a8c34ef63962097a1cde3ea48780b71d4a4e2dbb23dc571b1023</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>4E-BP1 protein</topic><topic>Adaptor Proteins, Signal Transducing</topic><topic>Carrier Proteins - metabolism</topic><topic>Cdc2 protein</topic><topic>CDC2 Protein Kinase - metabolism</topic><topic>Cell Cycle</topic><topic>eIF-4E binding protein 1</topic><topic>Eukaryotic Initiation Factor-4E</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>initiation factor eIF-4E</topic><topic>Peptide Initiation Factors - metabolism</topic><topic>Phosphoproteins - metabolism</topic><topic>Phosphorylation</topic><topic>Protein Biosynthesis</topic><topic>Repressor Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Heesom, Kate J.</creatorcontrib><creatorcontrib>Gampel, Alexandra</creatorcontrib><creatorcontrib>Mellor, Harry</creatorcontrib><creatorcontrib>Denton, Richard M.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Current biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Heesom, Kate J.</au><au>Gampel, Alexandra</au><au>Mellor, Harry</au><au>Denton, Richard M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cell cycle-dependent phosphorylation of the translational repressor eIF-4E binding protein-1 (4E-BP1)</atitle><jtitle>Current biology</jtitle><addtitle>Curr Biol</addtitle><date>2001-09-04</date><risdate>2001</risdate><volume>11</volume><issue>17</issue><spage>1374</spage><epage>1379</epage><pages>1374-1379</pages><issn>0960-9822</issn><eissn>1879-0445</eissn><abstract>A fundamental control point in the regulation of the initiation of protein synthesis is the formation of the eukaryotic initiation factor 4F (eIF-4F) complex. The formation of this complex depends upon the availability of the mRNA cap binding protein, eIF-4E, which is sequestered away from the translational machinery by the tight association of eIF-4E binding proteins (4E-BPs). Phosphorylation of 4E-BP1 is critical in causing its dissociation from eIF-4E, leaving 4E available to form translationally active eIF-4F complexes, switching on mRNA translation. In this report, we provide the first evidence that the phosphorylation of 4E-BP1 increases during mitosis and identify Ser-65 and Thr-70 as phosphorylated sites. Phosphorylation of Thr-70 has been implicated in the regulation of 4E-BP1 function, but the kinase phosphorylating this site was unknown. We show that the cyclin-dependent kinase, cdc2, phosphorylates 4E-BP1 at Thr-70 and that phosphorylation of this site is permissive for Ser-65 phosphorylation. 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| identifier | ISSN: 0960-9822 |
| ispartof | Current biology, 2001-09, Vol.11 (17), p.1374-1379 |
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| language | eng |
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| source | MEDLINE; Cell Press Archives; Elsevier ScienceDirect Journals; EZB Electronic Journals Library |
| subjects | 4E-BP1 protein Adaptor Proteins, Signal Transducing Carrier Proteins - metabolism Cdc2 protein CDC2 Protein Kinase - metabolism Cell Cycle eIF-4E binding protein 1 Eukaryotic Initiation Factor-4E HeLa Cells Humans initiation factor eIF-4E Peptide Initiation Factors - metabolism Phosphoproteins - metabolism Phosphorylation Protein Biosynthesis Repressor Proteins - metabolism |
| title | Cell cycle-dependent phosphorylation of the translational repressor eIF-4E binding protein-1 (4E-BP1) |
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