Interaction Of Cpn10 With NPAT Is Involved In Regulating Histone Transcription And S-Phase Progression

In mammalian cells, NPAT is a direct substrate of cyclinE-Cdk2 kinase and plays a critical role in activating histone gene transcription during the G1/S-phase transition and cell cycle progression. To further investigate mechanism of histone gene transcription, we carried out a yeast two hybrid assay by using the NPAT as a bait and identified Cpn10 as a new NPAT binding protein. Cpn10/HSPEl is a heat shock protein which is reported to localize to mitochondria. However, we found that in addition to mitochondria localization, Cpn10 exhibited partially co-localization with NPAT at a nuclear compartment called Cajal Body. Inhibiting Cpn10 expression disrupted the nuclear localization of NPAT without affecting Cajal Body formation. Importantly, a conserved LFD motif within Cpn10 is critical targeting NPAT and modulating histone gen transcription. Gain- and loss-of function experiments show that Cpn10 is important for S-phase progression and cell proliferation. Taken together, our findings reveal a novel role of Cpn10 in regulating histone gene transcription!...