Role of the UBL-UBA protein KPC2 in degradation of p27 at G1 phase of the cell cycle

Taichi Hara, Takumi Kamura, Shuhei Kotoshiba, Hidehisa Takahashi, Kenichiro Fujiwara, Ichiro Onoyama, Masahiro Shirakawa, Noboru Mizushima, Keiichi I. Nakayama

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

KPC2 (Kip1 ubiquitylation-promoting complex 2) together with KPC1 forms the ubiquitin ligase KPC, which regulates degradation of the cyclin-dependent kinase inhibitor p27 at the G1 phase of the cell cycle. KPC2 contains a ubiquitin-Iike (UBL) domain, two ubiquitin-associated (UBA) domains, and a heat shock chaperonin-binding (STI1) domain. We now show that KPC2 interacts with KPC1 through its UBL domain, with the 26S proteasome through its UBL and NH2-terminaI UBA domains, and with polyubiquitylated proteins through its UBA domains. The association of KPC2 with KPC1 was found to stabilize KPC1 in a manner dependent on the STI1 domain of KPC2. KPC2 mutants that lacked either the NH2-terminal or the COOH-terminal UBA domain supported the polyubiquitylation of p27 in vitro, whereas a KPC2 derivative lacking the STI1 domain was greatly impaired in this regard. Depletion of KPC2 by RNA interference resulted in inhibition of p27 degradation at the G1 phase, and introduction of KPC2 derivatives into the KPC2-depleted cells revealed that the NH2-terminal UBA domain of KPC2 is essential for p27 degradation. These observations suggest that ICPC2 cooperatively regulates p27 degradation with KPC1 and that the STI1 domain as well as the UBL and UBA domains of KPC2 are indispensable for its function.

Original languageEnglish
Pages (from-to)9292-9303
Number of pages12
JournalMolecular and Cellular Biology
Volume25
Issue number21
DOIs
Publication statusPublished - 2005 Nov
Externally publishedYes

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Ubiquitination
G1 Phase
Ubiquitin
Cell Cycle
Proteins
Cyclin-Dependent Kinase Inhibitor p27
Chaperonins
Ligases
RNA Interference
Shock
Hot Temperature

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Hara, T., Kamura, T., Kotoshiba, S., Takahashi, H., Fujiwara, K., Onoyama, I., ... Nakayama, K. I. (2005). Role of the UBL-UBA protein KPC2 in degradation of p27 at G1 phase of the cell cycle. Molecular and Cellular Biology, 25(21), 9292-9303. https://doi.org/10.1128/MCB.25.21.9292-9303.2005

Role of the UBL-UBA protein KPC2 in degradation of p27 at G1 phase of the cell cycle. / Hara, Taichi; Kamura, Takumi; Kotoshiba, Shuhei; Takahashi, Hidehisa; Fujiwara, Kenichiro; Onoyama, Ichiro; Shirakawa, Masahiro; Mizushima, Noboru; Nakayama, Keiichi I.

In: Molecular and Cellular Biology, Vol. 25, No. 21, 11.2005, p. 9292-9303.

Research output: Contribution to journalArticle

Hara, T, Kamura, T, Kotoshiba, S, Takahashi, H, Fujiwara, K, Onoyama, I, Shirakawa, M, Mizushima, N & Nakayama, KI 2005, 'Role of the UBL-UBA protein KPC2 in degradation of p27 at G1 phase of the cell cycle', Molecular and Cellular Biology, vol. 25, no. 21, pp. 9292-9303. https://doi.org/10.1128/MCB.25.21.9292-9303.2005
Hara, Taichi ; Kamura, Takumi ; Kotoshiba, Shuhei ; Takahashi, Hidehisa ; Fujiwara, Kenichiro ; Onoyama, Ichiro ; Shirakawa, Masahiro ; Mizushima, Noboru ; Nakayama, Keiichi I. / Role of the UBL-UBA protein KPC2 in degradation of p27 at G1 phase of the cell cycle. In: Molecular and Cellular Biology. 2005 ; Vol. 25, No. 21. pp. 9292-9303.
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