TTC4 provides a functional link between RASSF1C and DNA primase

Abstract

TTC4 protein was identified as a putative tumor suppressor since its gene is often mutated in some cancers. Also, its drosophila homologue was shown to interact with DNA primase (p180). Recently, we observed that murine TTC4 interacts with hampin, a component of MYST1 histone acetyltransferase complex. This interaction may provide a link between DNA primase (p180) and other tumor supressor proteins, such as RASSF1C, in the complex interactome network. We observed that in cultured 3T3 fibroblasts and other mammalian cell lines TTC4 localizes during cell cycle progression similarly to DNA primase (p180). In addition, the nuclear pool of endogenous TTC4 has a punctate pattern partly co‐localizing with endogenous RASSF1C and PML nuclear bodies.Upon overexpression, TTC4 has almost exclusive cytoplasmic localization and its transport to nucleus occurs only in the presence of overexpressed RASSF1C. Interestingly, overexpressed TTC4 with RASSF1C also co‐localize on microtubules. Therefore, RASSF1C appears to be required for nuclear sorting of TTC4. We propose that this regulation of TTC4 nuclear sorting by RASSF1C may be important for its association with DNA primase (p180) and, therefore, may constitute a part of unknown signaling pathway leading to regulation of DNA synthesis.