CEP192 interacts physically and functionally with the K63-deubiquitinase CYLD to promote mitotic spindle assembly

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• CEP192 is a vital centrosome protein essential for centrosome biogenesis and function across species.
• CEP192 depletion causes mitotic arrest with disorganized microtubules, indicating a role beyond centrosome activity in spindle assembly.
• Understanding CEP192's mitotic functions requires identifying its interacting partners.

Purpose of the Study:

• To identify proteins interacting with CEP192 to elucidate its role in mitosis.
• To investigate the functional relationship between CEP192 and its identified interacting partners in spindle formation.

Main Methods:

• Mass spectrometry was employed to identify CEP192-interacting proteins.
• Depletion studies (co-depletion of CEP192 and CYLD) were performed to assess functional relationships.
• Analysis of mitotic spindle assembly defects was conducted.

Main Results:

• CEP192 interacts with the K63-deubiquitinase CYLD, a microtubule-binding protein.
• Co-depletion of CYLD rescues the bipolar spindle assembly defects observed in CEP192-depleted cells.
• This suggests CYLD is involved in CEP192-mediated spindle formation.

Conclusions:

• CEP192 plays a direct role in regulating the mitotic microtubule landscape.
• CEP192 promotes robust mitotic spindle assembly by potentially regulating K63-polyubiquitin signaling via CYLD.
• This uncovers a novel function for CYLD in spindle formation and CEP192's broader role in mitosis.