Functional identification of the pro-apoptotic effector domain in human Sox4.
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.
Hur
Eun-Hye
EH
Research Institute of Molecular Genetics, Catholic Research Institutes of Medical Sciences, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
Hur
Wonhee
W
Choi
Ju-Youn
JY
Kim
In-Kyung
IK
Kim
Ho-Youn
HY
Yoon
Seung Kew
SK
Rhim
Hyangshuk
H
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D006609:High Mobility Group Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D055751:SOXC Transcription Factors; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
D006609:High Mobility Group Proteins; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors; D015534:Trans-Activators