A series of Ubiquitin Binding Factors Connects CDC48/p97 to Substrate Multiubiquitylation and Proteasomal Targeting

Cell, 120, 73-84

Speaker : 張儀君                                   Date : 2005’05’04 15:10~16:00

Commentator : 胥直利 老師                          Place : Room 601

Abstract

It is well known that priteolysis is pivotal for cellular and developmental regulation. Proteolysis is divided into two steps: substrate recognition and degradation. During the recognition step, the substrates are modified with ubiquitin by E1(ubiquitin-activating enzyme), E2(ubiquitin-conjugating enzyme), and E3(ubiquitin ligase). In the degradation step, the ubiquitylated substrate sort to the proteasome. There are several additional proteolytic factors such as CDC48, UFD1, UFD2, that are neither typical E2 or E3 nor component or regulators of proteasome. CDC48 is a member of ATPase family, which selectively segregate ubiquitylated proteins from other proteins of oligomeric protein complexes. UFD1 is a cofactor of CDC48. UFD2 possess a specific activity “E4 enzyme”, catalyze an extension of multiubiquitin chain in collaboration with E1, E2, and E3. RAD23, DSK2, and RPN10 are ubiquitin-conjugate binding proteins, and they function as receptors for ubiquitin-conjugates that ferry substrates to the proteasome. In this study, the author describe a pathway in which proteolytic substrates are guided to the proteasome by a succession of interacting factors. The data indicate that oligoubiquitylated substrate are first collected by CDC48^UFD1/NPL4 complex, then CDC48 recruits UFD2 to extend the ubiquitin chain. Subsequently, UFD2 recruit RAD23 (or DSK2); which binds the ubiquitin-protein conjugate and deliver it to the proteasome for degradation.

References

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