RNF11

RNF11 Full Name

ring finger protein 11

RNF11 Introduction

RNF11 (ring finger protein 11) is a small but versatile RING-H2-type E3 ubiquitin ligase that operates at the crossroads of several ubiquitin-dependent signaling circuits. The protein, which is only about 150 amino acids long, was identified through its interaction with AMSH, a deubiquitinating enzyme that regulates endosomal trafficking, and it later emerged as a component of the A20 ubiquitin-editing complex, the principal brake on NF-kB signaling. By cooperating with A20, RNF11 helps terminate inflammatory gene expression and prevents excessive immune activation. In parallel, RNF11 participates in the endosomal sorting of activated receptor tyrosine kinases, influencing how long growth factor receptors remain on the cell surface and, consequently, how strongly cells respond to mitogenic signals. Its expression is elevated in several tumor types, including breast and prostate cancer, and experimental manipulation of RNF11 levels alters cell growth, apoptosis, and sensitivity to inflammatory cytokines. Because it touches both inflammation and growth control, RNF11 is of interest as a molecular switch whose dysregulation may contribute to chronic inflammation and cancer.

Figure 1. RNF11 Gene (RING Finger Protein 11).

Structure, Ubiquitin Ligase Activity, and Interaction Partners
The defining feature of RNF11 is a RING-H2 finger that coordinates two zinc ions and confers E3 ubiquitin ligase activity, enabling the protein to attach ubiquitin to its substrates.
Flanking sequences support binding to partner proteins, and the overall small size of the protein suggests that it functions primarily as an adaptor that recruits substrates or ubiquitin-charged enzymes into larger complexes.
RNF11 was first cloned through its interaction with AMSH, an endosome-associated deubiquitinase, placing the ligase at the interface between ubiquitin conjugation and deubiquitination.
In the A20 ubiquitin-editing complex, RNF11 binds alongside the deubiquitinase A20 (TNFAIP3) and the E3 ligase ITCH, forming a regulatory hub that removes activating ubiquitin chains from signaling intermediates such as RIPK1 while adding degradative chains, thereby terminating NF-kB activation.
The RNF11 gene is located on chromosome 1, and the transcript is widely expressed, with particularly high levels in tissues enriched for immune and epithelial cells.
Subcellularly, RNF11 is found in the cytoplasm and at endosomal membranes, and its recruitment to ubiquitinated cargo is thought to be a key step in its endosomal functions.
Post-translational regulation of RNF11 itself, including ubiquitination and phosphorylation, tunes its stability and interactions in response to cellular stimuli.

Control of Inflammation, Receptor Trafficking, and Tumor Biology
In the innate immune system RNF11 acts as a negative feedback regulator: it is induced by inflammatory stimuli and then helps A20 dismantle NF-kB signaling, preventing uncontrolled expression of cytokines and chemokines.
Knockdown of RNF11 in cultured cells prolongs NF-kB activation after tumor necrosis factor stimulation and increases apoptosis susceptibility, illustrating its protective role against excessive inflammation.
At the endosome, RNF11 participates in the ubiquitin-dependent sorting of internalized receptors, such as the epidermal growth factor receptor, thereby controlling receptor downregulation and the duration of growth signaling.
Expression studies show that RNF11 is upregulated in breast, prostate, and other cancers, and its levels can influence tumor cell proliferation, invasion, and resistance to cytokine-mediated cell death.
Because RNF11 sits within both the NF-kB and receptor tyrosine kinase pathways, it has been proposed as a biomarker of inflammatory cancer microenvironments and as a candidate node for therapeutic intervention.
Understanding how RNF11 balances pro- and anti-inflammatory outputs in different cell types will be important for exploiting it as a drug target without disrupting normal immune homeostasis.

Alternate Names for RNF11

RNF11; ring finger protein 11; RING finger protein 11; CGI 123; MGC51169; Sid1669p; CGI-123; SID1669;