The proteasome is a multisubunit proteolytic enzyme comprising activator complexes bound to the 20 S catalytic core. The functions of the proteasomal activator (PA) 700 in ubiquitin/ATP-dependent protein degradation and of the PA28α/β activators in antigen presentation are well defined. However, the function of a third PA, PA28γ, remains elusive. We now show that mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK) kinase kinase 3 (MEKK3), a MAPK kinase kinase (MAPKKK) involved in MAPK kinase 7 (MKK7)–c-Jun N-terminal kinase (‘JNK’) and MKK6–p38 signalling, can bind PA28γ but not PA28α. In contrast, B-Raf, a MAPKKK specific for the MAPK/ERK kinase (‘MEK’)–ERK module, binds PA28γ and α. The PA28γ-binding domain of MEKK3 is located within its N-terminal regulatory domain (amino acids 1–178). Expression of MEKK3 in Cos-7 cells led to an increase in endogenous and co-expressed PA28γ protein levels, whereas kinase-deficient MEKK3 had no effect on PA28γ expression. Furthermore, in vitro assays indicated that PA28γ was a MEKK3 substrate. MEKK3 represents the first protein kinase capable of binding and phosphorylating a PA, and provides a potential mechanism to link stress-activated protein kinase signalling with the PA28γ-dependent proteasome.
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Research Article|
July 01 2003
MEKK3 interacts with the PA28gamma regulatory subunit of the proteasome
Carsten HAGEMANN;
Carsten HAGEMANN
1
∗Department of Cell Physiology and Pharmacology, University of Leicester, Medical Sciences Building, University Road, Leicester LE1 9HN, U.K.
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Rajnikant PATEL;
Rajnikant PATEL
†Department of Biochemistry, University of Leicester, Adrian Building, University Road, Leicester LE1 7RH, U.K.
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Jonathan L. BLANK
Jonathan L. BLANK
2
∗Department of Cell Physiology and Pharmacology, University of Leicester, Medical Sciences Building, University Road, Leicester LE1 9HN, U.K.
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Publisher: Portland Press Ltd
Received:
November 11 2002
Revision Received:
March 07 2003
Accepted:
March 21 2003
Accepted Manuscript online:
March 21 2003
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2003
2003
Biochem J (2003) 373 (1): 71–79.
Article history
Received:
November 11 2002
Revision Received:
March 07 2003
Accepted:
March 21 2003
Accepted Manuscript online:
March 21 2003
Citation
Carsten HAGEMANN, Rajnikant PATEL, Jonathan L. BLANK; MEKK3 interacts with the PA28gamma regulatory subunit of the proteasome. Biochem J 1 July 2003; 373 (1): 71–79. doi: https://doi.org/10.1042/bj20021758
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