Methylation of p53 by Set7/9 Mediates p53 Acetylation and Activity In Vivo
The protein methyltransferase Set7/9 was recently shown to regulate p53 activity in cancer cells. However, the impact of Set7/9 on p53 function in vivo is unclear. To explore these issues, we created a null allele of Set7/9 in mice. Cells from Set7/9 mutant mice fail to methylate p53 K369, are unabl...
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| Veröffentlicht in: | Molecular cell 2008-02, Vol.29 (3), p.392-400 |
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| creator | Kurash, Julia K. Lei, Hong Shen, Qiong Marston, Wendy L. Granda, Brian W. Fan, Hong Wall, Daniel Li, En Gaudet, François |
| description | The protein methyltransferase Set7/9 was recently shown to regulate p53 activity in cancer cells. However, the impact of Set7/9 on p53 function in vivo is unclear. To explore these issues, we created a null allele of
Set7/9 in mice. Cells from
Set7/9 mutant mice fail to methylate p53 K369, are unable to induce p53 downstream targets upon DNA damage, and are predisposed to oncogenic transformation. Importantly, we find that methylation of p53 by Set7/9 is required for the binding of the acetyltransferase Tip60 to p53 and for the subsequent acetylation of p53. We provide the first genetic evidence demonstrating that lysine methylation of p53 by Set7/9 is important for p53 activation in vivo and suggest a mechanistic link between methylation and acetylation of p53 through Tip60. |
| doi_str_mv | 10.1016/j.molcel.2007.12.025 |
| format | Article |
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Set7/9 in mice. Cells from
Set7/9 mutant mice fail to methylate p53 K369, are unable to induce p53 downstream targets upon DNA damage, and are predisposed to oncogenic transformation. Importantly, we find that methylation of p53 by Set7/9 is required for the binding of the acetyltransferase Tip60 to p53 and for the subsequent acetylation of p53. We provide the first genetic evidence demonstrating that lysine methylation of p53 by Set7/9 is important for p53 activation in vivo and suggest a mechanistic link between methylation and acetylation of p53 through Tip60.</description><subject>Acetylation</subject><subject>Acetyltransferases - metabolism</subject><subject>Animals</subject><subject>Cell Cycle - physiology</subject><subject>Cell Line</subject><subject>Cell Line, Transformed</subject><subject>Cell Transformation, Viral</subject><subject>CELLCYCLE</subject><subject>DNA Damage - genetics</subject><subject>Embryo, Mammalian - cytology</subject><subject>Fibroblasts - metabolism</subject><subject>Gene Dosage</subject><subject>Glutathione Transferase - metabolism</subject><subject>HCT116 Cells</subject><subject>Histone Methyltransferases</subject><subject>Histone-Lysine N-Methyltransferase - genetics</subject><subject>Histone-Lysine N-Methyltransferase - metabolism</subject><subject>Humans</subject><subject>Kidney - cytology</subject><subject>Lysine - metabolism</subject><subject>Methylation</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Mutation</subject><subject>Protein Methyltransferases - genetics</subject><subject>Protein Methyltransferases - metabolism</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><issn>1097-2765</issn><issn>1097-4164</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtOwzAQRS0EoqXwBwhlxa6p7Th-bJCqikdRKxY8tpbjTISrNCmxWyl_j0uL2LHx2KMzd-SD0DXBKcGET1bpuq0t1CnFWKSEppjmJ2hIsBJjRjg7Pd6p4PkAXXi_wpiwXKpzNCCSSkwZG6LnJYTPvjbBtU3SVskmz5KiT14hiIlKllA6E8D_tKcWwi9pmjK-g9u50CfzJvlwu_YSnVWm9nB1rCP0_nD_NnsaL14e57PpYmyZoGGcZaSQJcjc0oIbq-KRM6yqkkpTVoJxLokwinBKwOS05FYWWV6AElWlsIJshG4PuZuu_dqCD3rtfBRRmwbardcCUyUFzyLIDqDtWu87qPSmc2vT9ZpgvXeoV_rgUO8dakJ1dBjHbo7522IN5d_QUVoE7g4AxF_uHHTaWweNjbI6sEGXrft_wzcWf4Kv</recordid><startdate>20080215</startdate><enddate>20080215</enddate><creator>Kurash, Julia K.</creator><creator>Lei, Hong</creator><creator>Shen, Qiong</creator><creator>Marston, Wendy L.</creator><creator>Granda, Brian W.</creator><creator>Fan, Hong</creator><creator>Wall, Daniel</creator><creator>Li, En</creator><creator>Gaudet, François</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>7X8</scope></search><sort><creationdate>20080215</creationdate><title>Methylation of p53 by Set7/9 Mediates p53 Acetylation and Activity In Vivo</title><author>Kurash, Julia K. ; 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Set7/9 in mice. Cells from
Set7/9 mutant mice fail to methylate p53 K369, are unable to induce p53 downstream targets upon DNA damage, and are predisposed to oncogenic transformation. Importantly, we find that methylation of p53 by Set7/9 is required for the binding of the acetyltransferase Tip60 to p53 and for the subsequent acetylation of p53. We provide the first genetic evidence demonstrating that lysine methylation of p53 by Set7/9 is important for p53 activation in vivo and suggest a mechanistic link between methylation and acetylation of p53 through Tip60.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>18280244</pmid><doi>10.1016/j.molcel.2007.12.025</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acetylation Acetyltransferases - metabolism Animals Cell Cycle - physiology Cell Line Cell Line, Transformed Cell Transformation, Viral CELLCYCLE DNA Damage - genetics Embryo, Mammalian - cytology Fibroblasts - metabolism Gene Dosage Glutathione Transferase - metabolism HCT116 Cells Histone Methyltransferases Histone-Lysine N-Methyltransferase - genetics Histone-Lysine N-Methyltransferase - metabolism Humans Kidney - cytology Lysine - metabolism Methylation Mice Mice, Inbred C57BL Mice, Knockout Mutation Protein Methyltransferases - genetics Protein Methyltransferases - metabolism Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism |
| title | Methylation of p53 by Set7/9 Mediates p53 Acetylation and Activity In Vivo |
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