RASSF1

This gene encodes a protein similar to the RAS effector proteins. The RASSF1 gene has eight isoforms, of which RASSF1A and RASSF1C are the most abundantly expressed. These two isoforms are omnipresent in normal cells, where they localize microtubules and regulate cell growth. When expressed normally, RASSF1A causes repression of cyclin A2 and cyclin D1, leading to cell cycle arrest. RASSF1A also plays an important role in microtubule stability by inhibiting histone deacetylase 6 (HDAC6), leading to an increase in acetylated microtubules, which are more stable. RASSF1A binds to microtubule-associated proteins (MAPs) that regulate microtubule stability. RASSF1A also modulates apoptosis. Interaction of RASSF1A with K-Ras activates the apoptotic MST2-LATS1 pathway. RASSF1A is activated by mitogenic stimuli and K-Ras appears to be the major RASSF1A activator upon mitogenic stimulation. When RASSF1A is epigenetically inactivated, it leads to microtubule instability, suppression of apoptosis, and cell cycle progression, which promotes tumorigenesis. == Interactions ==

RASSF1 has been shown to interact with: • CNKSR1, • Death associated protein 6 • HRAS, • MAP1B, • MAP1S, and • RASSF5. == Pathology ==

Cervical cancer is known to be one of the most severe forms of cancer and is frequently associated with human papilloma virus (HPV). A few studies have been done to investigate the relationship between cervical cancers and RASSF1A, an isoform of RASSF1 that has been shown to suppress the proliferation in tumor cells. It is speculated that cancer subtypes may develop due to the inverse relationship of RASSF1A and HPV. RASSF1A promoter hypermethylation and oncogenic HPV were detected in ACs, but SCCs displayed a high level of HPV DNA and no RASSF1A promoter methylation. Another study used Hela cells to study the potential therapeutic effects of RASSF1A. Aberrant methylation of RASSF1A has also been found in breast, lung, gastric, liver, and colorectal cancer. == References ==