Subcellular localization of MTA proteins in normal and cancer cells.

Abstract

The subcellular localization of a protein is closely linked to and indicates its function. The metastatic tumor antigen (MTA) family has been under continuous investigation since its identification two decades ago. MTA1, MTA2, and MTA3 are the main members of the MTA family. MTA1, as the representative member of this family, has been shown to be widely expressed in both embryonic and adult tissues, as well as in normal and cancerous conditions, indicating that MTA1 has functions both in physiological and pathological contexts. MTA1 is expressed at a higher level in most cancers than in their normal tissue counterparts. Even in normal cells, MTA1 levels vary a great deal from tissue to tissue. Importantly, MTA1 shows a multiple localization pattern in the cell, as do MTA2 and MTA3. Different MTA components in different subcellular compartments may exert different molecular functions in the cell. Previous studies revealed that MTA1 and MTA2 are predominately localized to the nucleus, while MTA3 is observed in both the nucleus and cytoplasm. Recent studies have reported that MTA1 is located in the nucleus, cytoplasm, and the nuclear envelope. In the nucleus, MTA1 dynamically interacts with chromatin in a MTA1-K532 methylation-dependent manner, whereas cytoplasmic MTA1 binds to the microtubule skeleton. MTA1 also shows a dynamic distribution during the cell cycle. Further investigations are needed to identify the exact subcellular localizations of MTA proteins. We review the sub-cellular localization patterns of the MTA family members and give a comprehensive overview of their respective molecular activities in multiple contexts.