Nuclear membrane protein LAP2 beta mediates transcriptional repression alone and together with its binding partner GCL (germ-cell-less)

LAP2 beta is an integral membrane protein of the nuclear envelope involved in chromatin and nuclear architecture. Using the yeast two-hybrid system, w e have cloned a novel LAP2 beta -binding protein, mGCL, which contains a BT B/POZ domain and is the mouse homologue of the Drosophila germ-cell-less (G CL) protein. In Drosophila embryos, GCL was shown to be essential for germ cell formation and was localized to the nuclear envelope. Here, we show tha t, in mammalian cells, GCL is co-localized with LAP2 beta to the nuclear en velope. Nuclear fractionation studies reveal that mGCL acts as a nuclear ma trix component and not as an integral protein of the nuclear envelope. Rece ntly, mGCL was found to interact with the DP3 alpha component of the E2F tr anscription factor. This interaction reduced the transcriptional activity o f the E2F-DP heterodimer, probably by anchoring the complex to the nuclear envelope. We demonstrate here that LAP2 beta is also capable of reducing th e transcriptional activity of the E2F-DP complex and that it is more potent than mGCL in doing so. Co-expression of both LAP2 beta and mGCL with the E 2F-DP complex resulted in a reduced transcriptional activity equal to that exerted by the pRb protein.