CPNE1

CPNE1 Full Name

copine I

CPNE1 Introduction

CPNE1 encodes copine-1, the founding and most extensively studied member of the copine family of calcium-dependent phospholipid-binding proteins. The protein is characterized by a conserved domain architecture consisting of two N-terminal C2 domains, which mediate calcium-dependent translocation from the cytosol to the plasma membrane upon intracellular calcium elevation, and a C-terminal von Willebrand factor A (vWA) domain, which facilitates protein-protein interactions and may serve as an adaptor platform for assembling signaling complexes. This modular design enables CPNE1 to function as a calcium-regulated molecular switch at the membrane-cytoplasm interface, coupling transient calcium signals to downstream events including membrane trafficking, cytoskeletal reorganization, and transcriptional regulation. In neuronal progenitor cells, CPNE1 has been shown to promote differentiation through its C2 domains in a manner that can operate independently of calcium, suggesting dual calcium-dependent and calcium-independent regulatory modes.

In the context of human disease, CPNE1 has emerged as a significant oncogenic factor. It is overexpressed in multiple tumor types, most notably non-small cell lung cancer and prostate cancer, where elevated CPNE1 expression correlates with advanced TNM stage, lymph node metastasis, and unfavorable prognosis. Mechanistically, CPNE1 contributes to tumor progression through several interconnected pathways. It interacts with TNF-α receptor-associated signaling complexes to modulate NF-κB activation, thereby promoting cell survival and resistance to apoptosis. Additionally, CPNE1 influences cell cycle progression through regulation of cyclin expression and participates in epithelial-mesenchymal transition programs that facilitate metastatic dissemination. A pivotal study demonstrated that the E3 ubiquitin ligase NEDD4L targets CPNE1 for proteasomal degradation via ubiquitination at lysine residue K157, and that loss of NEDD4L function stabilizes CPNE1 protein, enhancing lung cancer cell proliferation and metastatic capacity. This NEDD4L-CPNE1 axis represents a therapeutically exploitable regulatory node, as restoring NEDD4L activity or disrupting CPNE1 stability could attenuate the malignant phenotype driven by CPNE1 overexpression.

Figure 1. The hypothetical model for the functional interplay of CPNE1 with NEDD4L in non-small-cell lung cancer cells. (Source: Zhang R, et al. 2021)

Alternate Names for CPNE1

CPNE1; copine I; CPN1; COPN1; copine-1;

• 1. Zhang R, et al. The regulation of CPNE1 ubiquitination by the NEDD4L is involved in the pathogenesis of non-small cell lung cancer. Cell Death Discov. 2021 Nov 6;7(1):336.
  2. Tang H, et al. The CPNE Family and Their Role in Cancers. Front Genet. 2021 Jul 23;12:689097.