TIP120A associates with unneddylated cullin 1 and regulates its neddylation.
The cullin-containing E3 ubiquitin ligases play an important role in regulating the abundance of key proteins involved in cellular processes such as cell cycle and cytokine signaling. We recently identified TIP120A as a cullin-interacting protein and found that TIP120A functions as a negative regulator of a ubiquitin ligase by interfering with the binding of Skp1 and an F box protein to CUL1. Here we show that TIP120A binds to the unneddylated CUL1 but not the neddylated one. The association of TIP120A with CUL1 requires both the N-terminal stalk and the C-terminal globular domain of CUL1. TIP120A efficiently inhibits neddylation of CUL1 but does not affect substrate-independent ubiquitination by CUL1/Rbx1, implying that it blocks the access of Nedd8 to the conjugation site but does not interfere with the interaction of the ubiquitin-conjugating enzyme with Rbx1. Our data suggest that the association/dissociation of TIP120A coupled to neddylation/deneddylation of CUL1 may play an important role in assembly and disassembly of Skp1-Cdc53/cullin-F box ubiquitin ligases.
Hwang
Ji-Won
JW
Department of Biochemistry, College of Science and Protein Network Research Center, Yonsei University, Seoul, South Korea.
Min
Kyoeng-Woo
KW
Tamura
Taka-aki
TA
Yoon
Jong-Bok
JB
D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D044842:Cullin Proteins; D006367:HeLa Cells; D006801:Humans; D008025:Ligases / Q000378:metabolism; D046911:Macromolecular Substances; D000075687:NEDD8 Protein; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism*
C486317:CAND1 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C100318:Cullin 1; D044842:Cullin Proteins; D046911:Macromolecular Substances; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; D014157:Transcription Factors; D014452:Ubiquitins; D044767:Ubiquitin-Protein Ligases; D008025:Ligases