Functional identification of the pro-apoptotic effector domain in human Sox4

Eun Hye Hur, Wonhee Hur, Ju Youn Choi, In Kyung Kim, Ho Youn Kim, Seung Kew Yoon, Hyangshuk Rhim

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38 Scopus citations

Abstract

Recent studies provide evidence that Sox4 is involved in regulating apoptosis as well as tumorigenesis of various human cancers; however, its role in the apoptotic machinery is not fully understood. Here we describe that the central domain containing glycine-rich region in Sox4, named CD, is a pivotal pro-apoptotic domain to induce apoptotic cell death. Deletion of the DNA-binding domain or trans-activation domain in Sox4 did not significantly affect pro-apoptotic activity, whereas transient transfection of the high mobility group box or the serine-rich region abrogated the apoptotic activity. Moreover, overexpression of the CD construct (aa 166-342) revealed the apoptotic activity comparable to that of wild-type Sox4, approximately 60% of cell death. Our data suggest that the apoptotic activity of Sox4 can be dissociated from its transcriptional trans-activation and is mediated through its CD.

Original languageEnglish
Pages (from-to)59-67
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume325
Issue number1
DOIs
StatePublished - 3 Dec 2004

Bibliographical note

Funding Information:
We thank H. Clevers for the pCDM7-Sox4 plasmid. This study was supported by the Korean Research Foundation (KRF-99-041-D000344), the 2002 Specialized Research Center grant from the Korean Science and Engineering Foundation to the Rheumatism Research Center at The Catholic University of Korea (R11-2002-098-04003-0), and Korea Institute of Science and Technology Evaluation and Planning and Ministry of Science and Technology, Korean government, through its National Nuclear Technology Program (2004).

Keywords

  • Apoptosis
  • DNA-binding domain
  • Glycine-rich region
  • High mobility group
  • Serine-rich region
  • Sox4
  • trans-Activation domain

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