Deficiency of Rap1-Binding Protein RAPL Causes Lymphoproliferative Disorders through Mislocalization of p27kip1

Koko Katagiri, Yoshihiro Ueda, Takashi Tomiyama, Kaneki Yasuda, Yoshinobu Toda, Susumu Ikehara, Keiichi Nakayama, Tatsuo Kinashi

研究成果: ジャーナルへの寄稿記事

21 引用 (Scopus)

抄録

RAPL (an alternative spliced form of Rassf5) is a critical Ras-related protein1 (Rap1) effector that regulates lymphocyte adhesion. Here, we have shown that in addition to this previously described function, RAPL also negatively controls lymphocyte proliferation and prevents autoimmunity and lymphoma. RAPL-deficient mice experienced age-related lupus-like glomerulonephritis and developed B cell lymphomas. RAPL-deficient lymphocytes showed hyperproliferation by enhanced S phase entry after antigen receptor ligation. Compared to wild-type cells, RAPL-deficient naive lymphocytes had a 2- to 3-fold increase in Cdk2 kinase activity with a cytoplasmic mislocalization of the cyclin-dependent kinase inhibitor p27kip1. RAPL was found to suppress the phosphorylation of p27kip1 on serine 10 (S10) and promoted p27kip1 nuclear translocation. An S10A mutation in p27kip1 corrected its cytoplasmic accumulation, reduced hyperproliferation in RAPL-deficient lymphocytes, and suppressed glomerulonephritis and development of B cell lymphoma. Thus, RAPL serves as a checkpoint for S phase entry to prevent lymphoproliferative disorders through the spatial regulation of p27kip1.

元の言語英語
ページ(範囲)24-38
ページ数15
ジャーナルImmunity
34
発行部数1
DOI
出版物ステータス出版済み - 1 28 2011

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Lymphoproliferative Disorders
Carrier Proteins
Lymphocytes
B-Cell Lymphoma
S Phase Cell Cycle Checkpoints
Lupus Nephritis
Antigen Receptors
Cyclin-Dependent Kinases
Glomerulonephritis
Autoimmunity
S Phase
Serine
Ligation
Lymphoma
Phosphotransferases
Phosphorylation
Mutation

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

これを引用

Katagiri, K., Ueda, Y., Tomiyama, T., Yasuda, K., Toda, Y., Ikehara, S., ... Kinashi, T. (2011). Deficiency of Rap1-Binding Protein RAPL Causes Lymphoproliferative Disorders through Mislocalization of p27kip1. Immunity, 34(1), 24-38. https://doi.org/10.1016/j.immuni.2010.12.010

Deficiency of Rap1-Binding Protein RAPL Causes Lymphoproliferative Disorders through Mislocalization of p27kip1. / Katagiri, Koko; Ueda, Yoshihiro; Tomiyama, Takashi; Yasuda, Kaneki; Toda, Yoshinobu; Ikehara, Susumu; Nakayama, Keiichi; Kinashi, Tatsuo.

:: Immunity, 巻 34, 番号 1, 28.01.2011, p. 24-38.

研究成果: ジャーナルへの寄稿記事

Katagiri, K, Ueda, Y, Tomiyama, T, Yasuda, K, Toda, Y, Ikehara, S, Nakayama, K & Kinashi, T 2011, 'Deficiency of Rap1-Binding Protein RAPL Causes Lymphoproliferative Disorders through Mislocalization of p27kip1', Immunity, 巻. 34, 番号 1, pp. 24-38. https://doi.org/10.1016/j.immuni.2010.12.010
Katagiri, Koko ; Ueda, Yoshihiro ; Tomiyama, Takashi ; Yasuda, Kaneki ; Toda, Yoshinobu ; Ikehara, Susumu ; Nakayama, Keiichi ; Kinashi, Tatsuo. / Deficiency of Rap1-Binding Protein RAPL Causes Lymphoproliferative Disorders through Mislocalization of p27kip1. :: Immunity. 2011 ; 巻 34, 番号 1. pp. 24-38.
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