Please use this identifier to cite or link to this item:
http://hdl.handle.net/11375/6253
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Capone, John P. | en_US |
dc.contributor.author | Piluso, David | en_US |
dc.date.accessioned | 2014-06-18T16:34:38Z | - |
dc.date.available | 2014-06-18T16:34:38Z | - |
dc.date.created | 2010-03-31 | en_US |
dc.date.issued | 2004-08 | en_US |
dc.identifier.other | opendissertations/1577 | en_US |
dc.identifier.other | 2116 | en_US |
dc.identifier.other | 1255731 | en_US |
dc.identifier.uri | http://hdl.handle.net/11375/6253 | - |
dc.description | HCF-l, a transcriptional regulatory protein, was originally identified as an accessory factor for the induction of Herpes Simplex Virus immediate-early genes by the viral transactivator VP16. Recently, HCF-1 has emerged as a chromatin-binding transcriptional co-regulator that plays an essential role in cellular proliferation. In order to further characterize the function of HCF-1 and determine the mechanisms by which it contributes to cellular proliferation we have sought to identify novel HCF-1 interaction partners and elucidate their function. In this thesis, we describe the identification of key cell cycle regulatory proteins, Miz-1 and E2F-4, as novel HCF-1 interaction partners. Miz-1, a transcription factor that activates transcription of cell cycle inhibitory genes, is an integral part of the anti-mitogenic TGF-β pathway and contributes to cell cycle arrest following DNA damage and differentiation signals. HCF-1 associates with the Miz-1 transactivation domain and antagonizes Miz-1-dependent transcriptional activation of p15INK4b, a cyclin-dependent kinase inhibitor, suggesting that HCF-1 can indirectly promote pRB family inactivation, and thus, cellular proliferation. E2F-4, a member of the E2F family of transcription factors that regulate cellular proliferation in conjunction with the retinoblastoma family of proteins, is involved in repression of E2F responsive genes at G0/G1 and consequently, cell cycle arrest or differentiation. Overexpression of E2F-4 suppresses HCF-1-mediated rescue of cellular proliferation, indicating an antagonistic role for these proteins in the cell cycle. Together, these findings contribute to identifying additional HCF-1 interaction partners and may provide insight into the molecular mechanism of HCF-1-mediated cell cycle progression. | en_US |
dc.description.abstract | <p>HCF-l, a transcriptional regulatory protein, was originally identified as an accessory factor for the induction of Herpes Simplex Virus immediate-early genes by the viral transactivator VPl6. Recently, HCF-1 has emerged as a chromatin-binding transcriptional co-regulator that plays an essential role in cellular proliferation. In order to further characterize the function of HCF-l and determine the mechanisms by which it contributes to cellular proliferation we have sought to identify novel HCF-1 interaction partners and elucidate their function. In this thesis, we describe the identification of key cell cycle regulatory proteins, Miz-1 and E2F-4, as novel HCF-1 interaction partners. Miz-1, a transcription factor that activates transcription of cell cycle inhibitory genes, is an integral part of the anti-mitogenic TGF-β pathway and contributes to cell cycle arrest following DNA damage and differentiation signals. HCF-1 associates with the Miz-1 transactivation domain and antagonizes Miz-1- dependent transcriptional activation of p15INK4b, a cyclin-dependent kinase inhibitor, suggesting that HCF-1 can indirectly promote pRB family inactivation, and thus, cellular proliferation. E2F-4, a member of the E2F family of transcription factors that regulate cellular proliferation in conjunction with the retinoblastoma family of proteins, is involved in repression of E2F responsive genes at GO/G1 and consequently, cell cycle arrest or differentiation. Overexpression of E2F-4 suppresses HCF-1-mediated rescue of cellular proliferation, indicating an antagonistic role for these proteins in the cell cycle. Together, these findings contribute to identifying additional HCF-1 interaction partners and may provide insight into the molecular mechanism of HCF-1-mediated cell cycle progression.</p> | en_US |
dc.subject | Biochemistry | en_US |
dc.subject | Biochemistry | en_US |
dc.title | Identification of cell cycle regulatory proteins that interact with HCF-1 | en_US |
dc.type | thesis | en_US |
dc.contributor.department | Biochemistry | en_US |
dc.description.degree | Doctor of Philosophy (PhD) | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Size | Format | |
---|---|---|---|
fulltext.pdf | 6.8 MB | Adobe PDF | View/Open |
Items in MacSphere are protected by copyright, with all rights reserved, unless otherwise indicated.