p27 deregulation by Skp2 overexpression induced by the JAK2V617 mutation

A. Furuhata, A. Kimura, K. Shide, K. Shimoda, M. Murakami, H. Ito, S. Gao, K. Yoshida, Y. Tagawa, K. Hagiwara, A. Takagi, T. Kojima, Motoshi Suzuki, A. Abe, T. Naoe, T. Murate

Research output: Contribution to journalArticle

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Abstract

Janus kinase 2 (JAK2) V617F mutation has been regarded as the major cause of myeloproliferative disorders (MPD). However, the mechanisms of abnormal cell growth by JAK2V617F have not been elucidated. In this study, cell cycle regulatory protein expression was analyzed using JAK2V617F-Ba/F3 and mock-Ba/F3. JAK2V617F-Ba/F3, but not mock-Ba/F3, showed IL-3 independent cell growth and constitutive STATs activation. Deregulation of p27 Kip1 , the cell cycle regulator at the G1 to S transition, was observed in JAK2V617F-Ba/F3 but not in mock-control. p27 Kip1 deregulation was not due to p27 Kip1 mRNA level but due to high Skp2 expression, a subunit of ubiquitin E3 ligase, through the STAT binding in the Skp2 promoter. Like JAK2V617F overexpression, constitutively active STAT5 or STAT3 induced aberrant p27 Kip1 expression of Ba/F3 cells. Similar findings were observed in BCR/ABL-transfected Ba/F3. Our results elucidate the regulatory mechanism by which JAK2V617F modulates Skp2 gene expression through the STAT transcription factors.

Original languageEnglish
Pages (from-to)411-416
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume383
Issue number4
DOIs
Publication statusPublished - 12-06-2009
Externally publishedYes

Fingerprint

Deregulation
Cell growth
STAT Transcription Factors
Janus Kinase 2
Cell Cycle Proteins
Mutation
Ubiquitin-Protein Ligases
Interleukin-3
Gene expression
Myeloproliferative Disorders
Chemical activation
Cells
Growth
Messenger RNA
Cell Cycle
Gene Expression

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Furuhata, A., Kimura, A., Shide, K., Shimoda, K., Murakami, M., Ito, H., ... Murate, T. (2009). p27 deregulation by Skp2 overexpression induced by the JAK2V617 mutation. Biochemical and Biophysical Research Communications, 383(4), 411-416. https://doi.org/10.1016/j.bbrc.2009.04.015
Furuhata, A. ; Kimura, A. ; Shide, K. ; Shimoda, K. ; Murakami, M. ; Ito, H. ; Gao, S. ; Yoshida, K. ; Tagawa, Y. ; Hagiwara, K. ; Takagi, A. ; Kojima, T. ; Suzuki, Motoshi ; Abe, A. ; Naoe, T. ; Murate, T. / p27 deregulation by Skp2 overexpression induced by the JAK2V617 mutation. In: Biochemical and Biophysical Research Communications. 2009 ; Vol. 383, No. 4. pp. 411-416.
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Furuhata, A, Kimura, A, Shide, K, Shimoda, K, Murakami, M, Ito, H, Gao, S, Yoshida, K, Tagawa, Y, Hagiwara, K, Takagi, A, Kojima, T, Suzuki, M, Abe, A, Naoe, T & Murate, T 2009, 'p27 deregulation by Skp2 overexpression induced by the JAK2V617 mutation', Biochemical and Biophysical Research Communications, vol. 383, no. 4, pp. 411-416. https://doi.org/10.1016/j.bbrc.2009.04.015

p27 deregulation by Skp2 overexpression induced by the JAK2V617 mutation. / Furuhata, A.; Kimura, A.; Shide, K.; Shimoda, K.; Murakami, M.; Ito, H.; Gao, S.; Yoshida, K.; Tagawa, Y.; Hagiwara, K.; Takagi, A.; Kojima, T.; Suzuki, Motoshi; Abe, A.; Naoe, T.; Murate, T.

In: Biochemical and Biophysical Research Communications, Vol. 383, No. 4, 12.06.2009, p. 411-416.

Research output: Contribution to journalArticle

TY - JOUR

T1 - p27 deregulation by Skp2 overexpression induced by the JAK2V617 mutation

AU - Furuhata, A.

AU - Kimura, A.

AU - Shide, K.

AU - Shimoda, K.

AU - Murakami, M.

AU - Ito, H.

AU - Gao, S.

AU - Yoshida, K.

AU - Tagawa, Y.

AU - Hagiwara, K.

AU - Takagi, A.

AU - Kojima, T.

AU - Suzuki, Motoshi

AU - Abe, A.

AU - Naoe, T.

AU - Murate, T.

PY - 2009/6/12

Y1 - 2009/6/12

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AB - Janus kinase 2 (JAK2) V617F mutation has been regarded as the major cause of myeloproliferative disorders (MPD). However, the mechanisms of abnormal cell growth by JAK2V617F have not been elucidated. In this study, cell cycle regulatory protein expression was analyzed using JAK2V617F-Ba/F3 and mock-Ba/F3. JAK2V617F-Ba/F3, but not mock-Ba/F3, showed IL-3 independent cell growth and constitutive STATs activation. Deregulation of p27 Kip1 , the cell cycle regulator at the G1 to S transition, was observed in JAK2V617F-Ba/F3 but not in mock-control. p27 Kip1 deregulation was not due to p27 Kip1 mRNA level but due to high Skp2 expression, a subunit of ubiquitin E3 ligase, through the STAT binding in the Skp2 promoter. Like JAK2V617F overexpression, constitutively active STAT5 or STAT3 induced aberrant p27 Kip1 expression of Ba/F3 cells. Similar findings were observed in BCR/ABL-transfected Ba/F3. Our results elucidate the regulatory mechanism by which JAK2V617F modulates Skp2 gene expression through the STAT transcription factors.

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