TELO2 interacting protein 1 (TTI1) is a protein that, as its name suggests, is known to interact with TELO2, a protein that is part of the TTT (TEL2, TTI1, TTI2) complex. This complex is involved in the regulation of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, which includes crucial proteins such as ATM, ATR, DNA-PK, mTOR, and SMG-1. These kinases are key players in cellular processes such as DNA damage response, cell cycle control, and nutrient sensing, which are vital for maintaining genomic stability and cellular metabolism.
TTI1, along with TTI2 and TELO2, is thought to be critical for the stability and functionality of these PIKKs. Specifically, the TTT complex assists in the assembly and stabilization of newly synthesized PIKKs, ensuring that they are properly folded and can effectively perform their enzymatic roles within the cell. Through its interaction with TELO2, TTI1 contributes to the recruitment and stabilization of chaperones such as HSP90, which are essential for the maturation of PIKK proteins.Mutations in the genes encoding the components of the TTT complex, including TTI1, can lead to defects in the PIKK signaling pathways and have been associated with a variety of developmental and degenerative disorders. These include microcephaly and primordial dwarfism, which are indicative of the complex's role in cell growth and division. Given the importance of PIKKs in responding to DNA damage, the TTT complex, and by extension TTI1, is also considered to be of significance in the context of cancer biology, as alterations in DNA repair mechanisms are a common feature in the development of cancer.
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