Ras association domain-containing protein 9 (RASSF9)

Ras association domain-containing protein 9 (RASSF9) is a scaffold-type protein encoded by the RASSF9 gene and is a member of the N-terminal RASSF family. It localizes to perinuclear endosomes and associates with peptidylglycine alpha-amidating monooxygenase, participating in intracellular trafficking and the regulation of cell differentiation. RASSF9 binds Ras family proteins (N-Ras, K-Ras, R-Ras), modulating downstream signaling pathways including MEK/ERK and, indirectly, p53 via interactions with ASPP proteins. It is essential for proper epidermal homeostasis, as evidenced by its role in keratinocyte growth suppression and initiation of differentiation (through induction of p21Cip1, filaggrin, and loricrin). In cancer, RASSF9 can have dual roles: promoting cell proliferation and tumor growth in non-small cell lung cancer (where it activates the MEK/ERK axis), but acting as a tumor suppressor in breast or gastric cancers, where its loss accelerates proliferation and suppresses apoptosis. Its expression is also regulated by environmental factors, such as sun-exposure in skin. While there are no drugs that target RASSF9 directly, inhibiting downstream effectors of its signaling cascade (MEK/ERK) can block its pro-proliferative effects in cancer cells

Other names

PAM CIPAMCIPCIP1P-CIP1PAM COOH-terminal interactor protein 1Peptidylglycine alpha-amidating monooxygenase COOH-terminal interactorRas association (RalGDS/AF-6) domain family (N-terminal) member 9

Inhibition of MEK/ERK signaling pathway blocks downstream effects of RASSF9-induced cell proliferation