; R o o t E n t r y F IDx @ C o m p O b j b W o r d D o c u m e n t + O b j e c t P o o l u u 2 3 4 5 6 7 8 9 : ; < F Microsoft Word 6.0 Document MSWordDoc Word.Document.6 ; 4 L 4 9523410 Feldherr Recently, we found that signal-mediated nuclear import varies as a function of cellular activity. Thus, as proliferating fibroblasts become quiescent there is a significant decrease in both the rate of macromolecular uptake into the nucleus, and the functional size of the transport channels. Conversely, nuclear import capacity increases above the proliferating level in rapidly dividing, SV40 transformed cells. These transport changes could have a significant effect on the regulation of transcriptional and translational events. Similarly, the modulation of nuclear efflux could play a fundamental role in controlling cell metabolism. Since substances exit the nucleus through the same transport channels that are used for uptake, and are subject to the same size restrictions, it is reasonable to assume that the import results mentioned above reflect overall transport activity. However, it is also possible that specific factor which enhance signal-mediated import have no effect on export. Therefore, considering its regulatory potential, we will investigate macromolecular movement out of the nucleus in transformed, quiescent, and dividing BALB/c cells. Relative efflux rates, as well as the size of particles that are able to exit the nucleus will be determined. This will be determined. This will be accomplished by injecting RNA- or polynucleotide-coated gold into the nucleoplasm and following its intracellular distribution by electron microscopy. To facilitate export, the gold preparations will be treated with oocyte nuclear extracts, or specific proteins that are known to be required for nuclear efflux. %%% This proposal will investigate the mechanisms by which components within the cell are transported across barrier (that is, the nuclear envelope) which separates the genetic material of the cell from the remainder of the cell (that is, the cytoplasm). The rate at which material is transported is a reflection of the level of metabolic activity of the cell, but the mechanism which controls this is not clear. A better understanding of this mechanism may allow researchers to cause a slow and quiescent cell to become an active cell. *** ; Oh +' 0 $ H l D h R:WWUSERTEMPLATENORMAL.DOT 9420795 toni douglas toni douglas @ ? @ S u m m a r y I n f o r m a t i o n ( 1 @ b @ F # Microsoft Word 6.0 3 ; e = e + j j j j j j j s 1 5 U T 3 s j s j j j j ~ j j j j m 9523410 Feldherr Recently, we found that signal-mediated nuclear import varies as a function of cellular activity. Thus, as proliferating fibroblasts become quiescent there is a significant decrease in both the rate of macromolecular uptake into the nucleus, and the functional size of the transport channels. Conversely, nuclear import capacity increases above the proliferating level in rapidly dividing, SV40 transformed cells. These transport changes could have a significant effect on the regulation of transcriptional and translational events. Similarly, the mo
