Cell division control protein 4

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Cell division control protein 4 (CDC4), also known as F-box/WD repeat-containing protein 7 (FBXW7), is a protein that in humans is encoded by the FBXW7 gene. This protein plays a crucial role in the regulation of the cell cycle and is involved in the ubiquitin-proteasome pathway, which is essential for the controlled degradation of various cellular proteins.

Function

CDC4 is a component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex. The SCF complex is responsible for the ubiquitination and subsequent proteasomal degradation of target proteins. CDC4 specifically recognizes phosphorylated substrates, leading to their ubiquitination and degradation. This process is vital for the regulation of the cell cycle, signal transduction, and other cellular processes.

Structure

CDC4 contains several important domains:

• The F-box domain, which is involved in protein-protein interactions and is essential for binding to SKP1.
• WD40 repeats, which are involved in the recognition of phosphorylated substrates.

Role in Cell Cycle

CDC4 plays a critical role in the progression of the cell cycle. It targets several key regulators of the cell cycle for degradation, including:

• Cyclin E, which is involved in the transition from the G1 phase to the S phase.
• c-Myc, a transcription factor that regulates cell growth and proliferation.
• Notch1, which is involved in cell differentiation and development.

By controlling the levels of these and other proteins, CDC4 ensures proper cell cycle progression and prevents uncontrolled cell proliferation.

Clinical Significance

Mutations in the FBXW7 gene have been implicated in various types of cancer. Loss of function mutations can lead to the stabilization of oncogenic proteins, contributing to tumorigenesis. FBXW7 mutations are frequently observed in cancers such as:

• Colorectal cancer
• Breast cancer
• T-cell acute lymphoblastic leukemia

Research and Therapeutic Potential

Given its role in the regulation of key cell cycle proteins, CDC4 is a potential target for cancer therapy. Research is ongoing to develop inhibitors that can modulate the activity of the SCF complex and restore normal cell cycle control in cancer cells.

See Also

• Ubiquitin-proteasome pathway
• Cell cycle
• SCF complex
• F-box protein