Proapoptotic Stimuli Induce Nuclear Accumulation of Glycogen Synthase Kinase-3β

Gautam N. Bijur, Richard S Jope

Research output: Contribution to journalArticle

174 Citations (Scopus)

Abstract

The goal of this study was to determine whether the intracellular distribution of the proapoptotic enzyme glycogen synthase kinase-3β (GSK-3β) is dynamically regulated by conditions that activate apoptotic signaling cascades. In untreated human neuroblastoma SH-SY5Y cells, GSK-3β was predominantly cytosolic, although a low level was also detected in the nucleus. The nuclear level of GSK-3β was rapidly increased after exposure of cells to serum-free media, heat shock, or staurosporine. Although each of these conditions caused changes in the serine 9 and/or tyrosine phosphorylation of GSK-3β, neither of these modifications was correlated with nuclear accumulation of GSK-3β. Heat shock and staurosporine treatments increased nuclear GSK-3β prior to activation of caspase-9 and caspase-3, and this nuclear accumulation of GSK-3β was unaltered by pretreatment with a general caspase inhibitor. The GSK-3β inhibitor lithium did not alter heat shock-induced nuclear accumulation of GSK-3β but increased the nuclear level of cyclin D1, indicating that cyclin D1 is a substrate of nuclear GSK-3β. Thus, the intracellular distribution of GSK-3β is dynamically regulated by signaling cascades, and apoptotic stimuli cause increased nuclear levels of GSK-3β, which facilitates interactions with nuclear substrates.

Original languageEnglish
Pages (from-to)37436-37442
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number40
DOIs
StatePublished - Oct 5 2001
Externally publishedYes

Fingerprint

Glycogen Synthase Kinase 3
Shock
Staurosporine
Hot Temperature
Cyclin D1
Phosphorylation
Caspase Inhibitors
Caspase 9
Serum-Free Culture Media
Substrates
Neuroblastoma
Lithium
Caspase 3
Serine
Tyrosine

ASJC Scopus subject areas

  • Biochemistry

Cite this

Proapoptotic Stimuli Induce Nuclear Accumulation of Glycogen Synthase Kinase-3β. / Bijur, Gautam N.; Jope, Richard S.

In: Journal of Biological Chemistry, Vol. 276, No. 40, 05.10.2001, p. 37436-37442.

Research output: Contribution to journalArticle

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