Degradation Mechanism of the Human Placenta-Specific Transcription Factor GCMa
Date Issued
2004
Date
2004
Author(s)
YANG, CHIH-SHENG
DOI
zh-TW
Abstract
Abstract
hGCMa, a member of glial cells missing (GCM) family, is specifically expressed in human placenta. By inducing the expression of the gene encoding the fusogenic protein, syncytin, hGCMa can regulate the fusion of cytotrophoblasts into the syncytiotrophoblast layer, which is essential for the formation of chorionic villous and pregnancy maintenance. Though several studies have been made to investigate the biological functions of hGCMa, little is known about how this transcription factor is regulated.
In this report, we demonstrate that hGCMa can be modified with polyubiquitin chains and degraded by the 26S proteasome in vivo. An F-box protein p50, the receptor component of the SCF E3 complex, was identified to interact with hGCMa in a phosphorylation-dependent manner. The GCM motif located at N-terminal fragment of hGCMa was found to be essential for interacting with p50. Furthermore, SCFp50 complex decreased the steady-state protein level of hGCMa in cells, but not the SCF complexes assembled with either F-box-deleted p50 or F-box protein p46. Meanwhile, cotransfection of hGCMa with F-box-deleted p50 or wild-type p50 repressed the transcriptional activity of hGCMa.
These results suggest that degradation of hGCMa is regulated by the ubiquitin-proteasome pathway and hGCMa is the first SCFp50 substrate ever been identified. In addition to mediating the degradation, p50 can also serve as a transcription co-repressor of hGCMa. Overall, this study reveals the degradation mechanism of hGCMa and may help understand how its transcriptional activity is controlled in vivo.
Subjects
蛋白降解機制
人類胎盤轉錄因子
the ubiquitin-proteasome pathway
human pacenta-specific transcription factor GCMa
Type
other
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