Mukhopadhyay Chandrani, Zhou Pengbo
Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, NY, USA.
Mol Cell Oncol. 2022 Feb 15;9(1):2030171. doi: 10.1080/23723556.2022.2030171. eCollection 2022.
Speckle-type POZ protein (SPOP), a Cullin 3-based ubiquitin ligase (CUL3), acts as a prostate-specific tumor suppressor. Loss-of-function mutations in SPOP occur in 10% of primary prostate cancer with a high Gleason grade and poor prognosis. However, it is unclear how the ubiquitin ligase activity of SPOP is controlled and how dysregulation of SPOP contributes to malignant transformation. Here, we identified GTPase Activating Protein (SH3 Domain) Binding Protein 1 (G3BP1) as an interactor and upstream regulator of CUL3, and it functions as an inhibitor of CUL3 ubiquitin ligase, suggesting a distinctive mode of CUL3 inactivation that aggravates prostate cancer.
斑点型POZ蛋白（SPOP）是一种基于Cullin 3的泛素连接酶（CUL3），作为前列腺特异性肿瘤抑制因子发挥作用。SPOP的功能丧失性突变发生在10%的原发性前列腺癌中，这些癌症具有高 Gleason 分级和不良预后。然而，目前尚不清楚SPOP的泛素连接酶活性是如何被控制的，以及SPOP的失调如何导致恶性转化。在这里，我们鉴定出GTP酶激活蛋白（SH3结构域）结合蛋白1（G3BP1）作为CUL3的相互作用因子和上游调节因子，它作为CUL3泛素连接酶的抑制剂发挥作用，提示一种加重前列腺癌的CUL3失活独特模式。
