Rolly protein (ROLP)-Epb4.1/3: a potential protein-protein interaction relevant for the maintenance of cell adhesion.

We recently described Rolly Protein (ROLP), a small protein synthesized by substrate-adherent cells in a broad range of tissues. In a first set of experiments performed taking advantage of bone forming tibial cartilage as an experimental model we showed that ROLP transcription is associated to cells in an active proliferation state, whereas its downregulation is observed when cell proliferation decreases. Taking advantage of siRNA technology we also documented the expression modulation of some apoptosis-related genes in ROLP-silenced cells. In this work we search for the possible molecular interactors of ROLP by using both the antibody array approach as well as the co-immunoprecipitation approach. Results suggest the occurrence of an interaction of ROLP with Erythrocyte membrane Protein Band 4.1/3 (Epb4.1/3), an oncosuppressor downregulated in tumor development and in metastatic tissues; in addition we report experimental results that keep in line also with a potential interaction of ROLP with other PDZ-containing proteins. We also present experimental evidences supporting a role played by ROLP in cell adhesion thus supporting the existence of a biologically relevant link between ROLP and Epb4.1/3. We here suggest that ROLP might exert its biological role cooperating with Epb4.1/3, a protein that is involved in biological pathways that are often inhibited in tumor metastasis. Given the role of Epb4.1/3 in contrasting cancerogenesis we think that its cooperation with ROLP might be relevant in cancer studies and deserves further investigation.