Ras Association Domain-Containing Protein 3 (RASSF3) is a member of the Ras association domain family (RASSF), which plays a crucial role in intracellular signal transduction pathways. This protein is encoded by the RASSF3 gene and is involved in various cellular processes, including tumor suppression and signal transduction.
The RASSF3 gene is located on chromosome 12 and encodes a protein that contains a Ras association (RA) domain. This domain is essential for binding to GTP-bound Ras, a member of the Ras superfamily of small GTPases . The RA domain facilitates the localization of RASSF3 to the plasma membrane, where it can interact with other signaling molecules to propagate downstream signaling events .
RASSF3 is primarily known for its role as a tumor suppressor. It is involved in the regulation of cell proliferation, apoptosis, and cell cycle progression. The protein exerts its tumor-suppressive effects through various mechanisms, including the modulation of the Hippo signaling pathway . The Hippo pathway is a critical regulator of organ size and tissue homeostasis, and its dysregulation is often associated with cancer development.
RASSF3, along with other members of the C-RASSF subclass (RASSF1-6), contains a C-terminal coiled-coil motif known as the Salvador/RASSF/Hippo (SARAH) domain . This domain is involved in interactions with mammalian Ste20-like kinases, which are core components of the Hippo pathway. By interacting with these kinases, RASSF3 can influence the activity of downstream effectors, such as the transcriptional co-activators YAP and TAZ, thereby regulating cell proliferation and apoptosis.
The expression of RASSF3 is frequently downregulated in various human cancers due to DNA hypermethylation . This epigenetic modification leads to the silencing of the RASSF3 gene, contributing to tumor progression and poor prognosis. Restoring the expression of RASSF3 in cancer cells has been shown to inhibit tumor growth and induce apoptosis, highlighting its potential as a therapeutic target.
Human recombinant RASSF3 is produced using recombinant DNA technology, which involves the insertion of the RASSF3 gene into an expression vector, followed by the expression of the protein in a suitable host system, such as E. coli or mammalian cells. The recombinant protein can be purified and used for various research applications, including studies on its function, mechanism of action, and potential therapeutic uses.