RASSF1
Description
The RASSF1 (Ras association domain family member 1) is a protein-coding gene located on chromosome 3.
RASSF1, also known as Ras association domain-containing protein 1, is a protein encoded by the RASSF1 gene in humans. It shares similarities with RAS effector proteins. RASSF1 has eight isoforms, with RASSF1A and RASSF1C being the most abundant. These isoforms are ubiquitously present in normal cells and localize to microtubules, regulating cell growth. RASSF1A normally represses cyclin A2 and cyclin D1, leading to cell cycle arrest. RASSF1A also contributes to microtubule stability by inhibiting HDAC6, promoting acetylation and stability of microtubules. RASSF1A interacts with microtubule-associated proteins (MAPs) that regulate microtubule stability. RASSF1A also plays a role in apoptosis, activating the MST2-LATS1 pathway through its interaction with K-Ras. RASSF1A is activated by mitogenic stimuli, with K-Ras appearing to be the major activator in response to such stimulation.
RASSF1 is a potential tumor suppressor that plays a critical role in apoptosis, particularly in response to death receptor activation. It activates MST2 and MST1 kinases during Fas-induced apoptosis by preventing their dephosphorylation. RASSF1, when associated with MOAP1, facilitates BAX conformational change and its translocation to mitochondrial membranes in response to TNF and TNFSF10 stimulation. Isoform A of RASSF1 interacts with CDC20, an activator of the anaphase-promoting complex (APC), leading to inhibition of APC activity and mitotic progression. It also inhibits cell proliferation by negatively regulating cell cycle progression at the G1/S phase by controlling cyclin D1 protein accumulation. Isoform C, however, lacks these functions, and its specific role remains undefined. Isoform A disrupts the interactions between MDM2, DAXX, and USP7, promoting MDM2 self-ubiquitination and the efficient activation of TP53 in response to DNA damage during cell-cycle checkpoint control.
RASSF1 is also known as 123F2, NORE2A, RASSF1A, RDA32, REH3P21.
