E3 ubiquitin-protein ligase DZIP3 (DZIP3)

E3 ubiquitin-protein ligase DZIP3 (DZIP3) is a zinc finger, RNA-binding, RING-type E3 ubiquitin ligase that mediates the attachment of ubiquitin to target proteins, leading to their proteasomal degradation or stabilization. DZIP3 is characterized by its ability to specifically interact with Cyclin D1 mRNA via an AU-rich element in the 3’UTR, thereby stabilizing Cyclin D1 transcripts, as well as by catalyzing post-translational K63-linked ubiquitination of Cyclin D1 protein to stabilize its levels in the G1 phase of the cell cycle. Overexpression of DZIP3 promotes cancer cell growth, migration, and invasion, and is associated with metastasis in multiple cancer models. In addition, DZIP3 collaborates with other E3 ligases such as Ring1B to regulate gene expression by controlling the 3D organization of chromatin and modulating histone H2A ubiquitination in embryonic stem cell differentiation. DZIP3 is both cytoplasmic and nuclear, and exhibits a unique combination of RNA-binding and E3 ligase domains, linking transcriptional, post-transcriptional, and post-translational regulatory processes. No drugs directly targeting DZIP3 are currently documented.

Other names

DAZ interacting zinc finger protein 3KIAA0675hRUL138PPP1R66DAZ-interacting protein 3RING-type E3 ubiquitin transferase DZIP3RNA-binding ubiquitin ligase of 138 kDahuman RNA-binding ubiquitin ligase of 138 kDaUURF2 ubiquitin ligaseprotein phosphatase 1 regulatory subunit 66zinc finger DAZ interacting protein 3RNA-binding RING-H2 protein-ubiquitin ligase

Ubiquitin ligase activity (facilitates K63-linked ubiquitination and stabilization of target proteins, especially Cyclin D1); modulates RNA stability through AU-rich element binding in 3’UTR of Cyclin D1 mRNA; orchestrates 3D chromatin reorganization to repress gene transcription