Deciphering the molecular mechanism associated with the interaction of TULP3 and Histone deacetylases, SIRT1 and SIRT2

Tubby-like protein-3 (TULP3), a member of the tubby family, is recognized for its role in ciliary trafficking, linking membrane-associated proteins to the intraflagellar transport complex A (IFT-A). Mammalian tubby family proteins (TULP1-4), featuring a C-terminal tubby domain, play crucial roles in intracellular transport, signaling, cell differentiation, and motility. TULP3 is also associated with renal and hepatic fibrocystic disease and liver, kidney, and heart degeneration. However, the modulation of TULP3 function and its interacting partners in the cell still need to be understood. Recent studies have indicated interactions between TULP3 and various proteins, including acetylating and deacetylating enzymes. In this study, we investigate the interaction of TULP3 with Sirtuins, SIRT1, and SIRT2 using biochemical and biophysical techniques. Our findings revealed that both the N- and C-terminal domains of TULP3 are necessary for the interaction with SIRT1 and SIRT2. Furthermore, we have identified that TULP3 is not a deacetylation substrate for SIRT1.