RASSF1A Human

Ras association domain-containing protein 1 (RASSF1) is a member of the Ras association domain family, which includes proteins that share structural similarities with Ras effector proteins . The RASSF1 gene is located on chromosome 3p21.3 and encodes multiple isoforms through alternative splicing . Among these isoforms, RASSF1A and RASSF1C are the most abundantly expressed .

RASSF1 proteins contain a Ras association (RA) domain, which is crucial for their interaction with Ras and Ras-like small GTPases . The RA domain is located at the C-terminus in most RASSF proteins, but in some isoforms, it is found at the N-terminus . Additionally, RASSF1A, the longest isoform, harbors a cysteine-rich diacylglycerol (DAG) or C1 lipid-binding domain . The RA domain shares structural similarities with the Ras-binding protein Raf, although RASSF1 proteins lack catalytic domains and function primarily as adaptors to recruit other proteins .

RASSF1A is a well-known tumor suppressor gene that plays a significant role in cell cycle control, apoptosis, cell migration, and mitosis regulation . It is involved in the repression of cyclin A2 and cyclin D1, leading to cell cycle arrest . RASSF1A also contributes to microtubule stability by inhibiting histone deacetylase 6 (HDAC6), resulting in increased acetylation of microtubules . Furthermore, RASSF1A interacts with microtubule-associated proteins (MAPs) to regulate microtubule stability and modulates apoptosis through the activation of the MST2-LATS1 pathway .

The inactivation of RASSF1A is frequently observed in various cancers, including lung, breast, kidney, and nasopharyngeal cancers . The primary mechanism of inactivation is the hypermethylation of its promoter region, leading to the loss of expression . RASSF1A is one of the most frequently silenced genes in over 40 types of cancer . The loss of RASSF1A expression disrupts its tumor suppressor functions, contributing to uncontrolled cell proliferation and tumor development .