Deleted in liver cancer 1 (DLC1) is a Rho-GTPase-activating protein (GAP) that is downregulated in various tumor types. In vitro, DLC1 specifically inactivates the small GTPases RhoA, RhoB and RhoC through its GAP domain and this appears to contribute to its tumor suppressor function in vivo. Molecular mechanisms that control DLC1 activity have not so far been investigated. Here, we show that phorbol-ester-induced activation of protein kinase C and protein kinase D stimulates association of DLC1 with the phosphoserine/phosphothreonine-binding 14-3-3 adaptor proteins via recognition motifs that involve Ser327 and Ser431. Association with 14-3-3 proteins inhibits DLC1 GAP activity and facilitates signaling by active Rho. We further show that treatment of cells with phorbol ester or coexpression of 14-3-3 proteins, blocks DLC1 nucleocytoplasmic shuttling, probably by masking a previously unrecognized nuclear localization sequence. The binding to 14-3-3 proteins is thus a newly discovered mechanism by which DLC1 activity is regulated and compartmentalized.

Abstract-We have demonstrated that back-end-of-line (BEOL)processing can successfully be performed in a university environment on die that have been fabricated at a foundry. This processing option enables universities to integrate state-of-the-art feature sizes with low resolution photolithography capabilities, such as achieved with a contact aligner, typically available at universities. With this capability, new device technologies and materials can be explored at the university level, where the basic research on the technology can occur without the timelines and expectations that are placed on product development in an industrial setting. By incorporating state-of-the-art feature sizes with these research efforts, the research results will be more applicable and more easily transferable to an industrial environment.In our project, we have demonstrated the integration of a foundry processed chip with the BEOL university processing through the fabrication of a small phase-change memory array with CMOS access transistors and addressing circuitry wherein the phase-change memory material was processed BEOL at Boise State University.