MACROMOLECULAR EXCHANGES ACROSS THE NUCLEAR ENVELOPE
The nuclear envelope represents the primary physical barrier between the major sites of transcription and translation in eucaryotic cells. As such, it has the potential of regulating cellular activity by controlling the intracellular distribution of macromolecules. In this regard we are interested in the permeability characteristics of envelopes to proteins and RNA. The pathways and mechanisms of exchange of these substances are being studied using a variety of biochemical, morphological, and immunological procedures. Specifically, three projects are currently in progress in our laboratory. First, we have established that there is a highly significant decrease in the nuclear import of macromolecules as proliferating cells become quiescent (enter the Go state), and we are investigating the factors (e.g., changes in pore composition and/or cytoplasmic components) that are responsible for these changes. Second, we have identified two Xenopus oocyte heat shock proteins that normally recycle between the nucleus and cytoplasm. Since there is very little information available concerning the efflux of proteins from the nucleus, we are attempting to characterize the signal sequence required for the export of these polypeptides. Third, nuclear transport capacity increases significantly in SV40 transformed cells. We have determined that this increase is caused by the SV40 large T antigen, and wish to identify the domain of the large T antigen that performs this function and mechanism involved.