Paired-like homeodomain protein ESXR1 possesses a cleavable C-terminal region that inhibits cyclin degradation

Oncogene
Heita OzawaMasanori Hatakeyama

Abstract

The eukaryotic cell cycle is regulated by sequential activation and inactivation of cyclin-cyclin-dependent kinase (Cdk) complexes. In this work, we screened human cDNAs that can rescue yeast Saccharomyces cerevisiae from lethality caused by ectopic expression of human cyclin E and isolated a cDNA encoding ESXR1, a paired-like homeodomain-containing protein with a unique C-terminal proline-rich repeat region. In adult tissues, ESXR1 is primarily expressed in the testis. We demonstrate that ESXR1 prevents degradation of ubiquitinated cyclins in human cells. Accordingly, elevation of ESXR1 level results in accumulation of cyclin A and cyclin B1 and thereby provokes M-phase arrest. In human cells, the 65-kDa full-length ESXR1 protein is capable of proteolytically processing into N-terminal 45-kDa and C-terminal 20-kDa fragments. The C-terminal fragment, containing a proline-rich repeat region, is localized to the cytoplasm and displays the ability to inhibit cyclin degradation. In contrast, the N-terminal fragment, containing a paired-like homeodomain, is localized exclusively in the nucleus, suggesting that it plays a role in transcription. Our results indicate that proteolytic processing of ESXR1 plays a role in concerted regula...Continue Reading

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Citations

Apr 21, 2005·Seminars in Cell & Developmental Biology·Filippo Del Bene, Joachim Wittbrodt
May 1, 2010·Reproduction : the Official Journal of the Society for the Study of Fertility·James A MacLean, Miles F Wilkinson
Mar 26, 2008·Biochemical and Biophysical Research Communications·Junta NakajimaMasanori Hatakeyama
Jun 26, 2007·Human Molecular Genetics·Xiaoxia Wang, Jianzhi Zhang

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