Presenilin-1 (PS-1) is the most causative Alzheimer gene product, and its function is not well understood. In an attempt to elucidate the function of PS-1, we screened a human brain cDNA library for PS-1-interacting proteins using the yeast two-hybrid system and isolated a novel protein containing a PSD-95/Dlg/ZO-1 (PDZ)-like domain. This novel PS-1-associated protein (PSAP) shares a significant similarity with a Caenorhabditis elegans protein of unknown function. Northern blot analysis revealed that PSAP is predominantly expressed in the brain. Deletion of the first four C-terminal amino acid residues of PS-1, which contain the PDZ domain-binding motif (Gln-Phe-Tyr-Ile), reduced the binding activity of PS-1 toward PSAP 4-fold. These data suggest that PS-1 may associate with a PDZ-like domain-containing protein in vivo and thus may participate in receptor or channel clustering and intracellular signaling events in the brain.

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Liver cancer is considered the sixth most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths worldwide. Currently, there is no specific and effective therapy for hepatocellular carcinoma. Therefore, developing novel diagnostic and therapeutic strategies against hepatocellular carcinoma is of paramount importance. Solute carrier family 6 member 8 (SLC6A8) encodes the solute carrier family 6-8 to transport creatine into cells in a Na+ and Cl-- dependent manner. SLC6A8 deficiency is characterized by intellectual disabilities, loss of speech, and behavioral abnormalities. Of concern, the association of SLC6A8 with hepatocellular carcinoma remains elusive. In this study, we revealed that SLC6A8 knockdown significantly induced apoptosis and suppressed the migration and invasion of Hep3B and Huh-7 cells. These findings depicted the vital role of SLC6A8 in the initiation and progression of human hepatocellular carcinoma.