Synergistic effects of the SAPK/JNK and the proteasome pathway on glial fibrillary acidic protein (GFAP) accumulation in Alexander disease.

Synergistic effects of the SAPK/JNK and the proteasome pathway on glial fibrillary acidic protein (GFAP) accumulation in Alexander disease. Research Abstract Details 

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Synergistic effects of the SAPK/JNK and the proteasome pathway on glial fibrillary acidic protein (GFAP) accumulation in Alexander disease. Abstract Text:

Guomei Tang,Zhiheng Xu,James E Goldman,

Protein aggregates in astrocytes that contain glial fibrillary acidic protein (GFAP), small heat shock proteins, and ubiquitinated proteins are termed Rosenthal fibers and characterize Alexander disease, a leukodystrophy caused by heterozygous mutations in GFAP. The mechanisms responsible for the massive accumulation of GFAP in Alexander disease remain unclear. In this study, we show that overexpression of both wild type and R239C mutant human GFAP led to cytoplasmic inclusions. GFAP accumulation also led to a decrease of proteasome activity and an activation of the MLK2-JNK pathway. In turn, the expression of activated mixed lineage kinases (MLKs) induced JNK activation and increased GFAP accumulation, whereas blocking the JNK pathway decreased GFAP accumulation. Activated MLK also inhibited proteasome function. A direct inhibition of proteasome function pharmacologically further activated JNK. Our data suggest a synergistic interplay between the proteasome and the SAPK/JNK pathway in the context of GFAP accumulation. Feedback interactions among GFAP accumulation, SAPK/JNK activation, and proteasomal hypofunction cooperate to produce further protein accumulation and cellular stress responses.

Synergistic effects of the SAPK/JNK and the proteasome pathway on glial fibrillary acidic protein (GFAP) accumulation in Alexander disease. Publishing Authors By Initials

G Tang,Z Xu,JE Goldman,

For similar macromolecular substances: multiprotein complexes: multienzyme complexes: proteasome endopeptidase complex research abstracts see: macromolecular substances: multiprotein complexes: multienzyme complexes: proteasome endopeptidase complex research

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Synergistic effects of the SAPK/JNK and the proteasome pathway on glial fibrillary acidic protein (GFAP) accumulation in Alexander disease. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The Journal of biological chemistry

VOLUME: 281

Page Numbers: 38634-43

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 10

MONTH: 10

YEAR: 2006

Synergistic effects of the SAPK/JNK and the proteasome pathway on glial fibrillary acidic protein (GFAP) accumulation in Alexander disease. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Synergistic effects of the SAPK/JNK and the proteasome pathway on glial fibrillary acidic protein (GFAP) accumulation in Alexander disease. Keywords Mesh Terms:

KEYWORDS: Proteasome Endopeptidase Complex

MESH TERMS: metabolism

Chemical & Substance for Abstract: Synergistic effects of the SAPK/JNK and the proteasome pathway on glial fibrillary acidic protein (GFAP) accumulation in Alexander disease. Information

Substance Name: Proteasome Endopeptidase Complex

Registry Number: EC 3.4.25.1

Grant and Affiliation Information for Synergistic effects of the SAPK/JNK and the proteasome pathway on glial fibrillary acidic protein (GFAP) accumulation in Alexander disease.

AFFILIATION: Department of Pathology and the Center for Neurobiology and Behavior, Columbia University, 630 W. 168th Street, New York, NY 10032, USA.

Country: United States

AGENCY: United States NINDS

GRANT: P01 NS 42803

ACRONYM: NS

MEDLINETA: J Biol Chem

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