Cytoplasmic ubiquitin ligase KPC regulates proteolysis of p27Kip1 at G1 phase

Takumi Kamura, Taichi Hara, Masaki Matsumoto, Noriko Ishida, Fumihiko Okumura, Shigetsugu Hatakeyama, Minoru Yoshida, Keiko Nakayama, Keiichi I. Nakayama

Research output: Contribution to journalArticle

317 Citations (Scopus)

Abstract

The cyclin-dependent kinase inhibitor p27Kip1 is degraded at the G0-G1 transition of the cell cycle by the ubiquitin-proteasome pathway. Although the nuclear ubiquitin ligase (E3) SCFSkp2 is implicated in p27Kip1 degradation, proteolysis of p27Kip1 at the G0-G1 transition proceeds normally in Skp2-/- cells. Moreover, p27Kip1 is exported from the nucleus to the cytoplasm at G0-G1 (refs 9-11). These data suggest the existence of a Skp2-independent pathway for the degradation of p27Kip1 at G1 phase. We now describe a previously unidentified E3 complex: KPC (Kip1 ubiquitination-promoting complex), consisting of KPC1 and KPC2. KPC1 contains a RING-finger domain, and KPC2 contains a ubiquitin-like domain and two ubiquitin-associated domains. KPC interacts with and ubiquitinates p27Kip1 and is localized to the cytoplasm. Overexpression of KPC promoted the degradation of p27Kip1, whereas a dominant-negative mutant of KPC1 delayed p27Kip1 degradation. The nuclear export of p27Kip1 by CRM1 seems to be necessary for KPC-mediated proteolysis. Depletion of KPC1 by RNA interference also inhibited p27Kip1 degradation. KPC thus probably controls degradation of p27Kip1 in G1 phase after export of the latter from the nucleus.

Original languageEnglish
Pages (from-to)1229-1235
Number of pages7
JournalNature Cell Biology
Volume6
Issue number12
DOIs
Publication statusPublished - 2004 Dec
Externally publishedYes

Fingerprint

Ubiquitination
G1 Phase
Ligases
Ubiquitin
Proteolysis
Cytoplasm
RING Finger Domains
Ubiquitin-Protein Ligases
Cell Nucleus Active Transport
Cyclin-Dependent Kinases
Proteasome Endopeptidase Complex
RNA Interference
Cell Cycle

ASJC Scopus subject areas

  • Cell Biology

Cite this

Kamura, T., Hara, T., Matsumoto, M., Ishida, N., Okumura, F., Hatakeyama, S., ... Nakayama, K. I. (2004). Cytoplasmic ubiquitin ligase KPC regulates proteolysis of p27Kip1 at G1 phase. Nature Cell Biology, 6(12), 1229-1235. https://doi.org/10.1038/ncb1194

Cytoplasmic ubiquitin ligase KPC regulates proteolysis of p27Kip1 at G1 phase. / Kamura, Takumi; Hara, Taichi; Matsumoto, Masaki; Ishida, Noriko; Okumura, Fumihiko; Hatakeyama, Shigetsugu; Yoshida, Minoru; Nakayama, Keiko; Nakayama, Keiichi I.

In: Nature Cell Biology, Vol. 6, No. 12, 12.2004, p. 1229-1235.

Research output: Contribution to journalArticle

Kamura, T, Hara, T, Matsumoto, M, Ishida, N, Okumura, F, Hatakeyama, S, Yoshida, M, Nakayama, K & Nakayama, KI 2004, 'Cytoplasmic ubiquitin ligase KPC regulates proteolysis of p27Kip1 at G1 phase', Nature Cell Biology, vol. 6, no. 12, pp. 1229-1235. https://doi.org/10.1038/ncb1194
Kamura T, Hara T, Matsumoto M, Ishida N, Okumura F, Hatakeyama S et al. Cytoplasmic ubiquitin ligase KPC regulates proteolysis of p27Kip1 at G1 phase. Nature Cell Biology. 2004 Dec;6(12):1229-1235. https://doi.org/10.1038/ncb1194
Kamura, Takumi ; Hara, Taichi ; Matsumoto, Masaki ; Ishida, Noriko ; Okumura, Fumihiko ; Hatakeyama, Shigetsugu ; Yoshida, Minoru ; Nakayama, Keiko ; Nakayama, Keiichi I. / Cytoplasmic ubiquitin ligase KPC regulates proteolysis of p27Kip1 at G1 phase. In: Nature Cell Biology. 2004 ; Vol. 6, No. 12. pp. 1229-1235.
@article{418cfdb74fb6418d81cab2b745126665,
title = "Cytoplasmic ubiquitin ligase KPC regulates proteolysis of p27Kip1 at G1 phase",
abstract = "The cyclin-dependent kinase inhibitor p27Kip1 is degraded at the G0-G1 transition of the cell cycle by the ubiquitin-proteasome pathway. Although the nuclear ubiquitin ligase (E3) SCFSkp2 is implicated in p27Kip1 degradation, proteolysis of p27Kip1 at the G0-G1 transition proceeds normally in Skp2-/- cells. Moreover, p27Kip1 is exported from the nucleus to the cytoplasm at G0-G1 (refs 9-11). These data suggest the existence of a Skp2-independent pathway for the degradation of p27Kip1 at G1 phase. We now describe a previously unidentified E3 complex: KPC (Kip1 ubiquitination-promoting complex), consisting of KPC1 and KPC2. KPC1 contains a RING-finger domain, and KPC2 contains a ubiquitin-like domain and two ubiquitin-associated domains. KPC interacts with and ubiquitinates p27Kip1 and is localized to the cytoplasm. Overexpression of KPC promoted the degradation of p27Kip1, whereas a dominant-negative mutant of KPC1 delayed p27Kip1 degradation. The nuclear export of p27Kip1 by CRM1 seems to be necessary for KPC-mediated proteolysis. Depletion of KPC1 by RNA interference also inhibited p27Kip1 degradation. KPC thus probably controls degradation of p27Kip1 in G1 phase after export of the latter from the nucleus.",
author = "Takumi Kamura and Taichi Hara and Masaki Matsumoto and Noriko Ishida and Fumihiko Okumura and Shigetsugu Hatakeyama and Minoru Yoshida and Keiko Nakayama and Nakayama, {Keiichi I.}",
year = "2004",
month = "12",
doi = "10.1038/ncb1194",
language = "English",
volume = "6",
pages = "1229--1235",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - Cytoplasmic ubiquitin ligase KPC regulates proteolysis of p27Kip1 at G1 phase

AU - Kamura, Takumi

AU - Hara, Taichi

AU - Matsumoto, Masaki

AU - Ishida, Noriko

AU - Okumura, Fumihiko

AU - Hatakeyama, Shigetsugu

AU - Yoshida, Minoru

AU - Nakayama, Keiko

AU - Nakayama, Keiichi I.

PY - 2004/12

Y1 - 2004/12

N2 - The cyclin-dependent kinase inhibitor p27Kip1 is degraded at the G0-G1 transition of the cell cycle by the ubiquitin-proteasome pathway. Although the nuclear ubiquitin ligase (E3) SCFSkp2 is implicated in p27Kip1 degradation, proteolysis of p27Kip1 at the G0-G1 transition proceeds normally in Skp2-/- cells. Moreover, p27Kip1 is exported from the nucleus to the cytoplasm at G0-G1 (refs 9-11). These data suggest the existence of a Skp2-independent pathway for the degradation of p27Kip1 at G1 phase. We now describe a previously unidentified E3 complex: KPC (Kip1 ubiquitination-promoting complex), consisting of KPC1 and KPC2. KPC1 contains a RING-finger domain, and KPC2 contains a ubiquitin-like domain and two ubiquitin-associated domains. KPC interacts with and ubiquitinates p27Kip1 and is localized to the cytoplasm. Overexpression of KPC promoted the degradation of p27Kip1, whereas a dominant-negative mutant of KPC1 delayed p27Kip1 degradation. The nuclear export of p27Kip1 by CRM1 seems to be necessary for KPC-mediated proteolysis. Depletion of KPC1 by RNA interference also inhibited p27Kip1 degradation. KPC thus probably controls degradation of p27Kip1 in G1 phase after export of the latter from the nucleus.

AB - The cyclin-dependent kinase inhibitor p27Kip1 is degraded at the G0-G1 transition of the cell cycle by the ubiquitin-proteasome pathway. Although the nuclear ubiquitin ligase (E3) SCFSkp2 is implicated in p27Kip1 degradation, proteolysis of p27Kip1 at the G0-G1 transition proceeds normally in Skp2-/- cells. Moreover, p27Kip1 is exported from the nucleus to the cytoplasm at G0-G1 (refs 9-11). These data suggest the existence of a Skp2-independent pathway for the degradation of p27Kip1 at G1 phase. We now describe a previously unidentified E3 complex: KPC (Kip1 ubiquitination-promoting complex), consisting of KPC1 and KPC2. KPC1 contains a RING-finger domain, and KPC2 contains a ubiquitin-like domain and two ubiquitin-associated domains. KPC interacts with and ubiquitinates p27Kip1 and is localized to the cytoplasm. Overexpression of KPC promoted the degradation of p27Kip1, whereas a dominant-negative mutant of KPC1 delayed p27Kip1 degradation. The nuclear export of p27Kip1 by CRM1 seems to be necessary for KPC-mediated proteolysis. Depletion of KPC1 by RNA interference also inhibited p27Kip1 degradation. KPC thus probably controls degradation of p27Kip1 in G1 phase after export of the latter from the nucleus.

UR - http://www.scopus.com/inward/record.url?scp=10344260649&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10344260649&partnerID=8YFLogxK

U2 - 10.1038/ncb1194

DO - 10.1038/ncb1194

M3 - Article

VL - 6

SP - 1229

EP - 1235

JO - Nature Cell Biology

JF - Nature Cell Biology

SN - 1465-7392

IS - 12

ER -