The Human Nuclear SRcyp Is a Cell Cycle-regulated Cyclophilin

Abstract

) are found only in organisms of the animal kingdom and share several structural and enzymatic features. The presence of serine/arginine (S/R) dipeptide repeats in their C-terminal tail suggests that these enzymes belong to the SR protein family involved in the regulation of gene expression. The function of this group of cyclophilins is currently unknown. However, their C-terminal tails contain a highly conserved polypeptide signature segment (the moca domain), which may well be involved in the functional regulation of these proteins. We report here the identification of five Cdc2-type phosphorylation sites gathered in and around the moca domain of SRcyp, a human cyclophilin belonging to the Moca family. The segment of SRcyp containing the identified sites is specifically phosphorylated in mitotic cells. This mitosis-specific phosphorylation was inhibited by treatment of the cells with roscovitine, a specific inhibitor of cyclin-dependent kinases, suggesting that the unknown activity of the moca domain of SRcyp requires mitotic regulation by the Cdc2-cyclin B kinase complex. The Cdc2-cyclin B complex was found to phosphorylate four of the five identified phosphorylation sites in vitro, providing further support for this possibility. Like many factors stored in nuclear speckles and involved in the regulation of gene expression, this nuclear cyclophilin displays a predominantly diffuse cytoplasmic distribution at the onset of mitosis. Only in late telophase is SRcyp recruited to the newly formed nuclei. The transit of SRcyp through mitotic interchromatin granule clusters, before re-entering the nucleus, suggests that the timing of the appearance of this cyclophilin in the telophasic nuclei is tightly coordinated with post-mitotic events. Human SRcyp is the first cell cycle-regulated cyclophilin to be described.

Functional Analysis of VopF Activity Required for Colonization in Vibrio cholerae

“…3B). PPIG is a nuclear protein that is cell cycle regulated (17). It demonstrates distinct nuclear/cytoplasmic distribution patterns during the cell cycle (17).…”

“…PPIG is a nuclear protein that is cell cycle regulated (17). It demonstrates distinct nuclear/cytoplasmic distribution patterns during the cell cycle (17). BCA3 and COMMD1 have been shown to repress NF-κB-dependent transcription (18, 19), and COMMD1 further accelerates the ubiquitination and degradation of NF-κB subunits (20).…”

Structural and Biochemical Characterization of the Human Cyclophilin Family of Peptidyl-Prolyl Isomerases

“…Cyclophilins have been implicated in diverse signaling pathways, including mitochondrial apoptosis [22],[23], RNA splicing [24],[25], and adaptive immunity [26]. However, the proteins that are substrates for cyclophilins in these pathways have not been identified.…”

Suppression of Coronavirus Replication by Cyclophilin Inhibitors

“…Cyps are peptidyl–prolyl isomerases (PPIases) with physiological functions that have been described for many years as including chaperone and foldase activities [6]. Cyps are thought to be involved in diverse signaling pathways, including mitochondrial apoptosis [7,8], RNA splicing [9,10], and adaptive immunity [11]. However, the proteins that act as substrates for Cyps in these pathways have not yet been identified.…”