Frequent SPOP mutation defines the molecular feature underlying one of seven sub-types of human prostate cancer (PrCa). However, it remains largely elusive how SPOP functions as a tumor suppressor in PrCa. Here, we report that SPOP suppresses stem cell traits of both embryonic stem cells and PrCa cells through promoting Nanog poly-ubiquitination and subsequent degradation. Mechanistically, Nanog, but not other pluripotency-determining factors including Oct4, Sox2, and Klf4, specifically interacts with SPOP via a conservative degron motif. Importantly, cancer-derived mutations in SPOP or at the Nanog-degron (S68Y) disrupt SPOP-mediated destruction of Nanog, leading to elevated cancer stem cell traits and PrCa progression. Notably, we identify the Pin1 oncoprotein as an upstream Nanog regulator that impairs its recognition by SPOP and thereby stabilizes Nanog. Thus, Pin1 inhibitors promote SPOP-mediated destruction of Nanog, which provides the molecular insight and rationale to use Pin1 inhibitor(s) for targeted therapies of PrCa patients with wild-type SPOP.
Pubmed ID: 30595538 RIS Download
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This monoclonal targets Human CD26
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View all literature mentionsThis polyclonal targets CCNA2
View all literature mentionsThis monoclonal targets c-Myc
View all literature mentionsThis polyclonal targets p27 (N-20)
View all literature mentionsThis monoclonal targets cyclin E (HE12)
View all literature mentionsThis monoclonal targets GST (91G1) Rabbit mAb
View all literature mentionsThis unknown targets Rabbit IgG, whole molecule
View all literature mentionsThis unknown targets ANTI-FLAG(R) M2 Affinity Gel
View all literature mentionsThis monoclonal targets α-tubulin
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets Vinculin
View all literature mentionsThis monoclonal targets HA.11 Clone 16B12 Purified
View all literature mentionsThis monoclonal targets Human CD26
View all literature mentionsThis monoclonal targets CD117
View all literature mentionsThis monoclonal targets CD26
View all literature mentionsThis isotype control targets Not Applicable
View all literature mentionsThis monoclonal targets CD49f (Integrin alpha 6)
View all literature mentionsThis polyclonal targets Mouse IgG (whole molecule)-Peroxidase antibody produced in goat
View all literature mentionsThis monoclonal targets Trop2 (EGP-1)
View all literature mentionsThis monoclonal targets GFP
View all literature mentionsThis polyclonal targets FLAG
View all literature mentionsThis isotype control targets Not Applicable
View all literature mentionsThis unknown targets Mouse IgG2A Alexa Fluor 488 Isotype Control (Clone 20102)
View all literature mentionsThis monoclonal targets CD24
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