SHARPIN regulates multiple signaling pathways in tumorigenesis. A: SHARPIN mediates p53 ubiquitination and rapid degradation by the proteasome, which promotes tumorigenesis. B: SHARPIN interacts with PRMT5 and activates SOX10, PAX3 and MITF, which promotes tumorigenesis. PRMT5 also regulates PAX3 and MITF and inhibits p53 in tumorigenesis. C: SHARPIN upregulates Rap, which promotes melanoma development through p38 and JNK/c-Jun signaling. D: SHARPIN can bind with PTEN, which mediates tumorigenesis through the PI3K/AKT signaling pathway. SOX10, SRY-box transcription factor 10; MITF, melanocyte inducing transcription factor; PAX3, paired box 3; PRMT5, protein arginine methyltransferase 5; SHARPIN, shank-associated RH domain interactor; Rap1, ras-associated protein 1; JNK, c-Jun N-terminal kinases; MDM2, mouse double minute 2 homolog; PTEN, phosphatase and tensin homologue deleted on chromosome 10; PIP3, phosphatidylinositol (3,4,5)-trisphosphate; PIP2, phosphatidylinositol (4,5)-bisphosphate; PI3K, phosphoinositide 3-kinases; p, phosphorylated; Ub, ubiquitinated.