ENC1

ENC1 Full Name

ectodermal-neural cortex 1 (with BTB-like domain)

ENC1 Introduction

ENC1, also known by aliases including NRPB and p53-induced protein 10 (PIG10), encodes a member of the kelch-related family of actin-binding proteins that is distinguished by its conserved BTB (Broad-Complex, Tramtrack, and Bric a brac) domain and C-terminal kelch repeats. The BTB domain mediates protein-protein interactions and enables ENC1 to assemble into the CUL3-RING ubiquitin ligase complex, where ENC1 functions as a substrate adaptor that recruits specific target proteins for ubiquitination and proteasomal degradation. The kelch repeat domains, in contrast, confer actin-binding capacity and contribute to cytoskeletal organization. ENC1 is robustly expressed in the developing and adult brain, where it localizes to the neuronal cell body and cytoskeleton, and its expression is dynamically regulated by p53 family members, oxidative stress, and diverse oncogenic signaling pathways. Through its role in the CUL3 ubiquitin ligase complex, ENC1 modulates the stability of key regulatory proteins and thereby influences cell fate decisions, stress responses, and malignant transformation.

Figure 1. Mechanistic map illustrating the role of ENC1 in promoting tumor progression through multiple signaling pathways and molecules. (Source: He L, et al. 2024)

A centrally important function of ENC1 is its negative regulation of Nrf2 (NF-E2-related factor 2), the master transcription factor orchestrating cellular antioxidant and cytoprotective responses. ENC1 suppresses Nrf2 expression at the translational level without affecting Nrf2 mRNA abundance or protein stability, thereby restraining the Nrf2-driven antioxidant program under basal conditions. In parallel, ENC1 has emerged as an oncogenic factor in multiple human malignancies. ENC1 is upregulated in colorectal cancer through the Wnt/β-catenin signaling pathway and promotes tumor cell proliferation and invasion; in breast cancer, ENC1 is driven by a super-enhancer and confers resistance to ionizing radiation, while also promoting metastatic dissemination through β-catenin/TCF complex activation; in ovarian cancer, high ENC1 expression correlates with adverse clinical outcomes, and its depletion suppresses cell proliferation, migration, and invasion. The convergent roles of ENC1 as an Nrf2 repressor and a promoter of malignant phenotypes position it as both a potential therapeutic target and a clinically relevant prognostic biomarker.

Alternate Names for ENC1

ENC1; ectodermal-neural cortex 1 (with BTB-like domain); NRPB; ectoderm-neural cortex protein 1; ENC 1; kelch like 37 (Drosophila); KLHL37; PIG10; TP53I10; kelch-like 35

• 1. He L, et al. The emerging role of ectodermal neural cortex 1 in cancer. Sci Rep. 2024 Jan 4;14(1):513.
  2. Wang XJ, et al. Ectodermal-neural cortex 1 down-regulates Nrf2 at the translational level. PLoS One. 2009;4(5):e5492.