E3 ubiquitin-protein ligase RNF152 (RNF152)

E3 ubiquitin-protein ligase RNF152 (RNF152) is a small, lysosome-localized, single-pass transmembrane RING finger protein with E3 ubiquitin ligase activity[1][2][3][6]. RNF152 is best known for its role as a negative regulator of the mTORC1 signaling pathway: under conditions such as amino acid starvation or absence of growth factors, it ubiquitinates small GTPases (e.g., RagA via K63-linked polyubiquitination, Rheb via monoubiquitination), thereby inhibiting mTORC1 activity and regulating cell growth and proliferation[3][6]. RNF152 also self-ubiquitinates, which regulates its own degradation[2]. Beyond mTORC1 regulation, RNF152 can suppress Wnt/β-catenin signaling and modulate inflammatory and developmental pathways, including neural crest formation and innate immune signaling—actions that can be dependent or independent of its enzymatic ligase activity[2]. Overexpression promotes apoptosis, making RNF152 functionally relevant to cell death, cancer, and possibly neurodegeneration[1][3]. It is associated with diseases including cancer, neurodegenerative diseases, and developmental disorders[3][5]. The identification and targeting of RNF152 is of growing interest for therapies modulating mTORC1- or Wnt-dependent pathologies.

Other names

Ring finger protein 152RING finger protein 152RING-type E3 ubiquitin transferase RNF152FLJ39176

Negative regulation of mTORC1 activity through ubiquitination of GDP-bound RagA (via K63 linkage) and GDP-bound Rheb (monoubiquitination), leading to inhibition of mTORC1 signaling[3][6] - Negative regulation of Wnt/β-catenin pathway by inhibiting Dishevelled polymerization (in some contexts, independent of ligase activity)[2] - Modulation of inflammatory signaling by facilitating MyD88 oligomerization (E3 activity-independent)[2]