Journal article
Physical and functional interactions between the Wwox tumor suppressor protein and the AP-2γ transcription factor
Cancer research (Chicago, Ill.), Vol.64(22), pp.8256-8261
2004
DOI: 10.1158/0008-5472.CAN-04-2055
PMID: 15548692
Abstract
The WWOX gene encodes a tumor suppressor WW domain-containing protein, Wwox. Alterations of WWOX have been demonstrated in multiple types of cancer, and introduction of Wwox into Wwox-negative tumor cells has resulted in tumor suppression and apoptosis. The Wwox protein contains two WW domains that typically bind proline-rich motifs and mediate protein-protein interactions. Recently, we have described functional cross-talk between the Wwox protein and the p53 homologue, p73. To further explore the biological function of Wwox, we investigated other interacting candidates. In this report, we demonstrate a physical and functional association between AP-2gamma transcription factor and the Wwox protein. AP-2gamma at 20q13.2 encodes a transcription factor and is frequently amplified in breast carcinoma. We show that Wwox binds to the PPPY motif of AP-2gamma via its first WW domain. Alterations of tyrosine 33 in the first WW domain of Wwox or the proline-rich motif in AP-2gamma dramatically reduce this interaction. In addition, our results demonstrate that Wwox expression triggers redistribution of nuclear AP-2gamma to the cytoplasm, hence suppressing its transactivating function. Our results suggest that Wwox tumor suppressor protein inhibits AP-2gamma oncogenic activity by sequestering it in the cytoplasm.
Details
- Title: Subtitle
- Physical and functional interactions between the Wwox tumor suppressor protein and the AP-2γ transcription factor
- Creators
- Rami I AQEILAN - Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, United StatesAlexey PALAMARCHUK - Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, United StatesRonald J WEIGEL - Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, United StatesJuan J HERRERO - AxCell Biosciences Corporation, Newtown, Pennsylvania, United StatesYuri PEKARSKY - Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, United StatesCarlo M CROCE - Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, United States
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.64(22), pp.8256-8261
- Publisher
- American Association for Cancer Research; Philadelphia, PA
- DOI
- 10.1158/0008-5472.CAN-04-2055
- PMID
- 15548692
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Language
- English
- Date published
- 2004
- Academic Unit
- Molecular Physiology and Biophysics; Anatomy and Cell Biology; Surgery; Biochemistry and Molecular Biology
- Record Identifier
- 9984024557402771
Metrics
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