Cancer Biomarker Discovery and Characterization: Establishing the ASPP1 Interactome and Characterizing the Proliferation Marker Ki67

Abstract

Cancer biomarkers represent a class of tools useful for diagnosis, prognosis, and treatment. The Apoptotic Stimulating Protein of p53 (ASPP1) and Ki67 proteins represent two cancer biomarkers. To better evaluate biomarker function and identify novel therapeutic/biomarker targets, the ASPP1 interactome was established. Both Deleted in Breast Cancer 1 (DBC1) and Extended Synaptotagmin 1 (ESYT1) were shown to interact with ASPP1 under mycoplasma-infected conditions. Therefore ASPP1 binds unique partners during bacterial infection, validating that cellular stress affects protein signaling. Ki67 is a massive proliferation antigen with very little of its function understood. Therefore, a bioinformatics approach was utilized to identify novel Ki67 sequences. Multiple domains and relationships were identified throughout metazoan Ki67 orthologs and these appeared to have undergone a massive evolutionary expansion during the development of placental mammals. This study has further characterized the ASPP1 and Ki67 biomarkers providing important insight to their function and therapeutic potential as cancer prognostic tools.