MafB protein stability is regulated by the JNK and ubiquitin-proteasome pathways

Hiroshi Tanahashi, Keiji Kito, Takashi Ito, Katsuji Yoshioka

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

MafB is a basic leucine zipper transcription factor that plays important roles in development and differentiation processes. During osteoclastogenesis, its expression is downregulated at the transcriptional level via the JNK and p38 MAP kinase pathways. In the present study, we demonstrated that MafB protein stability is regulated by JNK and identified a phosphorylation site, Thr62. The expression of a constitutively active form of JNK (a fusion protein MKK7α1-JNK1β1) promoted the degradation of MafB in COS7 cells, and a T62A substitution significantly reduced the instability of MafB. The introduction of a fourfold (T58A/T62A/S70A/S74A) substitution in an acidic transcription-activating domain almost protected the instability resulting from the activation of JNK. Furthermore, treatment with proteasome inhibitors increased the MafB level, and a high-molecular-weight smear, characteristic of polyubiquitination, was observed in lysates from cells in which MafB, ubiquitin, and MKK7α1-JNK1β1 were co-expressed. These results suggest that phosphorylation of MafB by JNK confers susceptibility to proteasomal degradation.

Original languageEnglish
Pages (from-to)94-100
Number of pages7
JournalArchives of Biochemistry and Biophysics
Volume494
Issue number1
DOIs
Publication statusPublished - Feb 1 2010

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MafB Transcription Factor
Protein Stability
Proteasome Endopeptidase Complex
Ubiquitin
Phosphorylation
Basic-Leucine Zipper Transcription Factors
Proteasome Inhibitors
MAP Kinase Signaling System
p38 Mitogen-Activated Protein Kinases
Substitution reactions
Osteogenesis
Degradation
Down-Regulation
Molecular Weight
Transcription
Fusion reactions
Chemical activation
Molecular weight
Proteins

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

MafB protein stability is regulated by the JNK and ubiquitin-proteasome pathways. / Tanahashi, Hiroshi; Kito, Keiji; Ito, Takashi; Yoshioka, Katsuji.

In: Archives of Biochemistry and Biophysics, Vol. 494, No. 1, 01.02.2010, p. 94-100.

Research output: Contribution to journalArticle

Tanahashi, Hiroshi ; Kito, Keiji ; Ito, Takashi ; Yoshioka, Katsuji. / MafB protein stability is regulated by the JNK and ubiquitin-proteasome pathways. In: Archives of Biochemistry and Biophysics. 2010 ; Vol. 494, No. 1. pp. 94-100.
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