Cullin-2

Cullin-2 (CUL2) is a protein that in humans is encoded by the CUL2 gene. It is a member of the Cullin family of proteins, which are involved in the ubiquitin-proteasome system, a critical pathway for protein degradation and regulation within the cell.

Structure

Cullin-2 is a scaffold protein that forms part of the Cullin-RING ubiquitin ligase (CRL) complex. The CRL complex is responsible for the ubiquitination of target proteins, marking them for degradation by the proteasome. The structure of Cullin-2 includes a central cullin domain that interacts with other components of the CRL complex, including the RING-box protein RBX1 and various substrate recognition modules.

Function

Cullin-2 plays a crucial role in the regulation of various cellular processes through its involvement in the ubiquitin-proteasome system. It is particularly important in the regulation of the cell cycle, signal transduction, and transcription. By mediating the ubiquitination and subsequent degradation of specific target proteins, Cullin-2 helps maintain cellular homeostasis and prevents the accumulation of damaged or misfolded proteins.

Interactions

Cullin-2 interacts with several other proteins to form functional CRL complexes. These interactions include binding with Elongin B, Elongin C, and VHL (von Hippel-Lindau tumor suppressor). The VHL protein is a key component of the CRL complex that targets hypoxia-inducible factor (HIF) for degradation, thereby playing a role in the cellular response to oxygen levels.

Clinical Significance

Mutations or dysregulation of the CUL2 gene and its associated pathways can lead to various diseases, including cancer. The VHL-CUL2 complex is particularly significant in the context of von Hippel-Lindau disease, a hereditary condition associated with an increased risk of certain types of tumors.

See Also

• Cullin family
• Ubiquitin-proteasome system
• Cullin-RING ubiquitin ligase
• Proteasome
• RBX1
• Elongin B
• Elongin C
• VHL
• Hypoxia-inducible factor
• Von Hippel-Lindau disease