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60S ribosomal protein L8 (RPL8) is a structural protein encoded by the RPL8 gene that forms part of the large 60S ribosomal subunit in eukaryotes[3][4][5]. It binds 5S rRNA and is located at the aminoacyl-tRNA binding and peptidyltransferase center, contributing to the ribosome’s ability to synthesize proteins by facilitating elongation and tRNA function[1][2][4]. RPL8 is strongly expressed in most tissues as a component of the protein synthesis machinery[4]. In cancer, particularly liver cancer, its overexpression is associated with increased tumor cell viability, migration, invasion, and glycolysis, primarily via mTORC1 pathway activation[2]. Inhibition of RPL8 suppresses these oncogenic processes, yields enhanced apoptosis, and marks cells for ferroptosis, making RPL8 both a potential cancer therapeutic target and a biomarker for disease progression and treatment response[2][3]. Dysfunction or mutations in RPL8 are also linked to rare diseases such as Diamond-Blackfan anemia and spermatogenic failure 2[3]. Post-translational modifications (e.g., hydroxylation by NO66) further regulate its ribosomal function[2].
Most studied mechanism is gene silencing or inhibition, which suppresses mTORC1 pathway and oncogenic activity in cancer, promoting apoptosis[2][7]. Targeting may lead to reduced cell proliferation and increased cell death (e.g., ferroptosis).
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