Signal Transduction Involving the Dmp1 Transcription Factor and its Alteration in Human Cancer
Summary Dmp1 (cyclin D-interacting myb-like protein 1; also called Dmtf1) is a transcription factor that has been isolated in a yeast two-hybrid screen through its binding property to cyclin D2. Dmp1 directly binds to and activates the Arf promoter and induces Arf-p53-dependent cell cycle arrest in...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2008-01-01
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| Series: | Clinical Medicine Insights: Oncology |
| Online Access: | https://doi.org/10.4137/CMO.S548 |
| _version_ | 1818145266347278336 |
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| author | Takayuki Sugiyama Donna P. Frazier Pankaj Taneja Robert D. Kendig Rachel L. Morgan Lauren A. Matise Sarah J. Lagedrost Kazushi Inoue |
| author_facet | Takayuki Sugiyama Donna P. Frazier Pankaj Taneja Robert D. Kendig Rachel L. Morgan Lauren A. Matise Sarah J. Lagedrost Kazushi Inoue |
| author_sort | Takayuki Sugiyama |
| collection | DOAJ |
| description | Summary Dmp1 (cyclin D-interacting myb-like protein 1; also called Dmtf1) is a transcription factor that has been isolated in a yeast two-hybrid screen through its binding property to cyclin D2. Dmp1 directly binds to and activates the Arf promoter and induces Arf-p53-dependent cell cycle arrest in primary cells. D-type cyclins usually inhibit Dmp1-mediated transcription in a Cdk-independent fashion; however, Dmp1 shows synergistic effects with D-cyclins on the Arf promoter. Ras or Myc oncogene-induced tumor formation is accelerated in both Dmp1 +/- and Dmp1 -/- mice with no significant differences between Dmp1 +/- and Dmp1 -/- . Thus, Dmp1 is haplo-insufficient for tumor suppression. Tumors from Dmp1 -/- or Dmp1 +/- mice often retain wild-type Arf and p53 , suggesting that Dmp1 is a physiological regulator of the Arf-p53 pathway. The Dmp1 promoter is activated by oncogenic Ras-Raf signaling, while it is repressed by physiological mitogenic stimuli, overexpression of E2F proteins, and genotoxic stimuli mediated by NF-κB. The human DMP1 gene (h DMP1 ) is located on chromosome 7q21 and is hemizygously deleted in approximately 40% of human lung cancers, especially those that retain normal INK4a/ARF and P53 loci. Thus, h DMP1 is clearly involved in human carcinogenesis, and tumors with h DMP1 deletion may constitute a discrete disease entity. |
| first_indexed | 2024-12-11T12:00:43Z |
| format | Article |
| id | doaj.art-6a2c82e498194e2aae4623d27d65aee8 |
| institution | Directory Open Access Journal |
| issn | 1179-5549 |
| language | English |
| last_indexed | 2024-12-11T12:00:43Z |
| publishDate | 2008-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Clinical Medicine Insights: Oncology |
| spelling | doaj.art-6a2c82e498194e2aae4623d27d65aee82022-12-22T01:08:05ZengSAGE PublishingClinical Medicine Insights: Oncology1179-55492008-01-01210.4137/CMO.S548Signal Transduction Involving the Dmp1 Transcription Factor and its Alteration in Human CancerTakayuki Sugiyama0Donna P. Frazier1Pankaj Taneja2Robert D. Kendig3Rachel L. Morgan4Lauren A. Matise5Sarah J. Lagedrost6Kazushi Inoue7Cancer Biology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, N.C. 27157-0001, U.S.A.Cancer Biology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, N.C. 27157-0001, U.S.A.Cancer Biology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, N.C. 27157-0001, U.S.A.Cancer Biology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, N.C. 27157-0001, U.S.A.Cancer Biology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, N.C. 27157-0001, U.S.A.Cancer Biology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, N.C. 27157-0001, U.S.A.Cancer Biology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, N.C. 27157-0001, U.S.A.Cancer Biology, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, N.C. 27157-0001, U.S.A.Summary Dmp1 (cyclin D-interacting myb-like protein 1; also called Dmtf1) is a transcription factor that has been isolated in a yeast two-hybrid screen through its binding property to cyclin D2. Dmp1 directly binds to and activates the Arf promoter and induces Arf-p53-dependent cell cycle arrest in primary cells. D-type cyclins usually inhibit Dmp1-mediated transcription in a Cdk-independent fashion; however, Dmp1 shows synergistic effects with D-cyclins on the Arf promoter. Ras or Myc oncogene-induced tumor formation is accelerated in both Dmp1 +/- and Dmp1 -/- mice with no significant differences between Dmp1 +/- and Dmp1 -/- . Thus, Dmp1 is haplo-insufficient for tumor suppression. Tumors from Dmp1 -/- or Dmp1 +/- mice often retain wild-type Arf and p53 , suggesting that Dmp1 is a physiological regulator of the Arf-p53 pathway. The Dmp1 promoter is activated by oncogenic Ras-Raf signaling, while it is repressed by physiological mitogenic stimuli, overexpression of E2F proteins, and genotoxic stimuli mediated by NF-κB. The human DMP1 gene (h DMP1 ) is located on chromosome 7q21 and is hemizygously deleted in approximately 40% of human lung cancers, especially those that retain normal INK4a/ARF and P53 loci. Thus, h DMP1 is clearly involved in human carcinogenesis, and tumors with h DMP1 deletion may constitute a discrete disease entity.https://doi.org/10.4137/CMO.S548 |
| spellingShingle | Takayuki Sugiyama Donna P. Frazier Pankaj Taneja Robert D. Kendig Rachel L. Morgan Lauren A. Matise Sarah J. Lagedrost Kazushi Inoue Signal Transduction Involving the Dmp1 Transcription Factor and its Alteration in Human Cancer Clinical Medicine Insights: Oncology |
| title | Signal Transduction Involving the Dmp1 Transcription Factor and its Alteration in Human Cancer |
| title_full | Signal Transduction Involving the Dmp1 Transcription Factor and its Alteration in Human Cancer |
| title_fullStr | Signal Transduction Involving the Dmp1 Transcription Factor and its Alteration in Human Cancer |
| title_full_unstemmed | Signal Transduction Involving the Dmp1 Transcription Factor and its Alteration in Human Cancer |
| title_short | Signal Transduction Involving the Dmp1 Transcription Factor and its Alteration in Human Cancer |
| title_sort | signal transduction involving the dmp1 transcription factor and its alteration in human cancer |
| url | https://doi.org/10.4137/CMO.S548 |
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