CUL1

CUL1 Full Name

cullin 1

CUL1 Introduction

CUL1 (cullin 1) is a core scaffold protein of the SKP1-CUL1-F-box (SCF) E3 ubiquitin ligase complex, a pivotal regulator of protein homeostasis in eukaryotic cells. By serving as the structural backbone of SCF complexes, CUL1 coordinates the assembly of substrate recognition subunits (F-box proteins) with the catalytic RBX1 protein, enabling selective polyubiquitination of target proteins for subsequent 26S proteasome-mediated degradation. This process underlies the precise control of key cellular functions, including cell cycle progression, DNA replication, apoptosis, oxidative stress response, differentiation, stem cell maintenance, circadian rhythm regulation, and immune signaling, highlighting CUL1's central role in maintaining cellular integrity and homeostasis.

Functionally, CUL1 contributes to genome stability by mediating the timely degradation of regulatory proteins that govern DNA damage repair and chromosomal segregation. SCF complexes containing CUL1 target multiple cell cycle regulators, such as cyclins, cyclin-dependent kinase inhibitors, and transcription factors, ensuring accurate replication and partitioning of genetic material. Dysregulation of CUL1, whether through mutations, altered expression, or impaired neddylation, can compromise the ubiquitin-proteasome system, leading to genomic instability, uncontrolled proliferation, and aberrant cellular differentiation. Consequently, CUL1's activity is indispensable not only for normal cellular physiology but also for safeguarding against malignant transformation.

Clinically, aberrations in CUL1 and its SCF complex are strongly implicated in various cancers and other diseases. Genetic alterations in CUL1 occur across multiple tumor types, including colorectal, endometrial, gastric, and lung cancers, often correlating with poor prognosis. Moreover, CUL1 is a critical substrate for neddylation, a post-translational modification that activates SCF ligase function; disruption of CUL1 neddylation has been explored as a therapeutic strategy to suppress tumor growth, especially in lung cancer. Targeted modulation of CUL1, either through small molecules inhibiting its neddylation or by restoring SCF complex functionality, represents a promising avenue for cancer therapy, emphasizing its potential as both a biomarker and a druggable target.

Alternate Names for CUL1

CUL1; cullin 1; MGC149834; MGC149835; cullin-1; CUL-1; OTTHUMP00000202347

• 1.Zeng X, et al.; SKP1-CUL1-F-box: Key molecular targets affecting disease progression. FASEB J. 2025, 39(2):e70326.
  2.Chang HR. RNF126, 168 and CUL1: The Potential Utilization of Multi-Functional E3 Ubiquitin Ligases in Genome Maintenance for Cancer Therapy. Biomedicines. 2023, 11(9):2527.