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Molecular and Cellular Biology, January 2002, p. 453-468, Vol. 22, No. 2
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.22.2.453-468.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
Nucleocytoplasmic Shuttling of p130/RBL2: Novel Regulatory Mechanism
Anton Chestukhin, Larisa Litovchick, Katherine Rudich, and James A. DeCaprio*
Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115
Received 25 May 2001/
Returned for modification 9 July 2001/
Accepted 22 October 2001
The retinoblastoma-related pocket proteins pRb, p107, and p130 are implicated in the control of cell proliferation, differentiation, and transformation. The function of pocket proteins is in part mediated by their ability to inhibit specific E2F transcription factors. The transcriptional activity of E2Fs is controlled by alteration of their nucleocytoplasmic localization during the cell cycle. p130 was observed to shuttle between the nucleus and cytoplasm in a heterokaryon fusion assay, suggesting the presence of nuclear and cytoplasmic localization signals. Two independent nuclear localization signals (NLS) that could target reporter proteins to the nucleus in transient transfection and microinjection experiments were identified in the C terminus of p130. In addition to the C-terminal NLS, the intact pocket domain of p130 itself was sufficient for nuclear translocation. Moreover, an additional functional NLS was mapped within the unique Loop region of p130. An N-terminal domain that conferred cytoplasmic localization was identified. Removal of the entire N terminus did not affect the ability of p130 to interact with E2F and to induce growth arrest. A model suggesting that the activity of pRb family members can be regulated by intracellular trafficking of the proteins is proposed.
* Corresponding author. Mailing address: Dana-Farber Cancer Institute, Mayer 457, 44 Binney St., Boston, MA 02115. Phone: (617) 632-3825. Fax: (617) 632-4760. E-mail:
james_decaprio{at}dfci.harvard.edu.
Molecular and Cellular Biology, January 2002, p. 453-468, Vol. 22, No. 2
0022-538X/01/$04.00+0 DOI: 10.1128/MCB.22.2.453-468.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.
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