Proapoptotic Function of the Retinoblastoma Tumor Suppressor Protein
The retinoblastoma protein (pRB) tumor suppressor blocks cell proliferation by repressing the E2F transcription factors. This inhibition is relieved through mitogen-induced phosphorylation of pRB, triggering E2F release and activation of cell-cycle genes. E2F1 can also activate proapoptotic genes in...
| Main Authors: | , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Elsevier
2014
|
| Online Access: | http://hdl.handle.net/1721.1/84669 https://orcid.org/0000-0001-9451-2194 |
| _version_ | 1826194378068066304 |
|---|---|
| author | Ianari, Alessandra Natale, Tiziana Calo, Eliezer Ferretti, Elisabetta Alesse, Edoardo Screpanti, Isabella Haigis, Kevin M. Gulino, Alberto Lees, Jacqueline |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Ianari, Alessandra Natale, Tiziana Calo, Eliezer Ferretti, Elisabetta Alesse, Edoardo Screpanti, Isabella Haigis, Kevin M. Gulino, Alberto Lees, Jacqueline |
| author_sort | Ianari, Alessandra |
| collection | MIT |
| description | The retinoblastoma protein (pRB) tumor suppressor blocks cell proliferation by repressing the E2F transcription factors. This inhibition is relieved through mitogen-induced phosphorylation of pRB, triggering E2F release and activation of cell-cycle genes. E2F1 can also activate proapoptotic genes in response to genotoxic or oncogenic stress. However, pRB's role in this context has not been established. Here we show that DNA damage and E1A-induced oncogenic stress promote formation of a pRB-E2F1 complex even in proliferating cells. Moreover, pRB is bound to proapoptotic promoters that are transcriptionally active, and pRB is required for maximal apoptotic response in vitro and in vivo. Together, these data reveal a direct role for pRB in the induction of apoptosis in response to genotoxic or oncogenic stress. |
| first_indexed | 2024-09-23T09:55:03Z |
| format | Article |
| id | mit-1721.1/84669 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:55:03Z |
| publishDate | 2014 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/846692022-09-30T17:40:12Z Proapoptotic Function of the Retinoblastoma Tumor Suppressor Protein Ianari, Alessandra Natale, Tiziana Calo, Eliezer Ferretti, Elisabetta Alesse, Edoardo Screpanti, Isabella Haigis, Kevin M. Gulino, Alberto Lees, Jacqueline Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Ianari, Alessandra Calo, Eliezer Lees, Jacqueline The retinoblastoma protein (pRB) tumor suppressor blocks cell proliferation by repressing the E2F transcription factors. This inhibition is relieved through mitogen-induced phosphorylation of pRB, triggering E2F release and activation of cell-cycle genes. E2F1 can also activate proapoptotic genes in response to genotoxic or oncogenic stress. However, pRB's role in this context has not been established. Here we show that DNA damage and E1A-induced oncogenic stress promote formation of a pRB-E2F1 complex even in proliferating cells. Moreover, pRB is bound to proapoptotic promoters that are transcriptionally active, and pRB is required for maximal apoptotic response in vitro and in vivo. Together, these data reveal a direct role for pRB in the induction of apoptosis in response to genotoxic or oncogenic stress. National Institutes of Health (U.S.) (Grant 2-P01-CA42063) 2014-02-07T14:53:13Z 2014-02-07T14:53:13Z 2009-03 2008-08 Article http://purl.org/eprint/type/JournalArticle 15356108 http://hdl.handle.net/1721.1/84669 Ianari, Alessandra, Tiziana Natale, Eliezer Calo, Elisabetta Ferretti, Edoardo Alesse, Isabella Screpanti, Kevin Haigis, Alberto Gulino, and Jacqueline A. Lees. “Proapoptotic Function of the Retinoblastoma Tumor Suppressor Protein.” Cancer Cell 15, no. 3 (March 2009): 184-194. Copyright © 2009 Elsevier Inc. https://orcid.org/0000-0001-9451-2194 en_US http://dx.doi.org/10.1016/j.ccr.2009.01.026 Cancer Cell Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier Open Archive |
| spellingShingle | Ianari, Alessandra Natale, Tiziana Calo, Eliezer Ferretti, Elisabetta Alesse, Edoardo Screpanti, Isabella Haigis, Kevin M. Gulino, Alberto Lees, Jacqueline Proapoptotic Function of the Retinoblastoma Tumor Suppressor Protein |
| title | Proapoptotic Function of the Retinoblastoma Tumor Suppressor Protein |
| title_full | Proapoptotic Function of the Retinoblastoma Tumor Suppressor Protein |
| title_fullStr | Proapoptotic Function of the Retinoblastoma Tumor Suppressor Protein |
| title_full_unstemmed | Proapoptotic Function of the Retinoblastoma Tumor Suppressor Protein |
| title_short | Proapoptotic Function of the Retinoblastoma Tumor Suppressor Protein |
| title_sort | proapoptotic function of the retinoblastoma tumor suppressor protein |
| url | http://hdl.handle.net/1721.1/84669 https://orcid.org/0000-0001-9451-2194 |
| work_keys_str_mv | AT ianarialessandra proapoptoticfunctionoftheretinoblastomatumorsuppressorprotein AT nataletiziana proapoptoticfunctionoftheretinoblastomatumorsuppressorprotein AT caloeliezer proapoptoticfunctionoftheretinoblastomatumorsuppressorprotein AT ferrettielisabetta proapoptoticfunctionoftheretinoblastomatumorsuppressorprotein AT alesseedoardo proapoptoticfunctionoftheretinoblastomatumorsuppressorprotein AT screpantiisabella proapoptoticfunctionoftheretinoblastomatumorsuppressorprotein AT haigiskevinm proapoptoticfunctionoftheretinoblastomatumorsuppressorprotein AT gulinoalberto proapoptoticfunctionoftheretinoblastomatumorsuppressorprotein AT leesjacqueline proapoptoticfunctionoftheretinoblastomatumorsuppressorprotein |