SPOC1: a novel PHD-containing protein modulating chromatin structure and mitotic chromosome condensation.
In this study, we characterize the molecular and functional features of a novel protein called SPOC1. SPOC1 RNA expression was previously reported to be highest in highly proliferating tissues and increased in a subset of ovarian carcinoma patients, which statistically correlated with poor prognosis and residual disease. These observations implied that SPOC1 might play a role in cellular proliferation and oncogenesis. Here we show that the endogenous SPOC1 protein is labile, primarily chromatin associated and its expression as well as localization are regulated throughout the cell cycle. SPOC1 is dynamically regulated during mitosis with increased expression levels and biphasic localization to mitotic chromosomes indicating a functional role of SPOC1 in mitotic processes. Consistent with this postulate, SPOC1 siRNA knockdown experiments resulted in defects in mitotic chromosome condensation, alignment and aberrant sister chromatid segregation. Finally, we have been able to show, using micrococcal nuclease (MNase) chromatin-digestion assays that SPOC1 expression levels proportionally influence the degree of chromatin compaction. Collectively, our findings show that SPOC1 modulates chromatin structure and that tight regulation of its expression levels and subcellular localization during mitosis are crucial for proper chromosome condensation and cell division.
Kinkley
Sarah
S
Heinrich-Pette Institute for Experimental Virology and Immunology, Martinistrasse 52, 20251 Hamburg, Germany.
Staege
Hannah
H
Mohrmann
Gerrit
G
Rohaly
Gabor
G
Schaub
Theres
T
Kremmer
Elisabeth
E
Winterpacht
Andreas
A
Will
Hans
H
D000818:Animals; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism*; D002877:Chromosomes, Human / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D005057:Eukaryotic Cells; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008677:Metaphase; D008938:Mitosis; D011418:Prophase; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*
D002843:Chromatin; D004268:DNA-Binding Proteins; C503048:PHF13 protein, human; D034741:RNA, Small Interfering; D014157:Transcription Factors; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D046988:Proteasome Endopeptidase Complex