CPAP/CENPJ is essential for the stability and function of AAA+ ATPase VPS4B

Function of CENPJ/CPAP is essential for centriole duplication and cilia biogenesis. Recently, we showed that CPAP is also an integral Endosomal Sorting Complexes Required for Transport (ESCRT)-0-like protein that recruits ESCRT-I protein TSG101 to early endosome (EE) and positively regulates multi-vesicular body (MVB) formation. Sequential recruitment of the ESCRT protein complexes and AAA+ ATPase VPS4B to EE facilitates MVB biogenesis. VPS4B is critical for ESCRT-III disassembly/recycling and contributes to membrane fission in several cellular processes. Here, we report that CPAP is critical for the protein stability and EE localization of VPS4B, and this function is independent from its role as an ESCRT-0. Other VPS4B-dependent cellular processes such as exosome release, cytokinesis, and retroviral budding are also compromised under CPAP deficiency. Interaction with CPAP prevents the proteasome degradation of VPS4B. The stability and EE localization of VPS4B can be attributed to two different C-terminal domains in CPAP. Overall, these observations provide evidence that CPAP is critical for VPS4B function and suggest that distinct pools of CPAP may be involved in its ESCRT-0 and VPS4B stabilization roles.