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Cdk5 mediates changes in morphology and promotes apoptosis of astrocytoma cells in response to heat shock.

Publication ,  Journal Article
Gao, C; Negash, S; Wang, HS; Ledee, D; Guo, H; Russell, P; Zelenka, P
Published in: J Cell Sci
March 2001

The cyclin-dependent kinase member, Cdk5, is expressed in a variety of cell types, but neuron-specific expression of its activator, p35, is thought to limit its activity to neurons. Here we demonstrate that both Cdk5 and p35 are expressed in the human astrocytoma cell line, U373. Cdk5 and p35 are present in the detergent-insoluble cytoskeletal fraction of this cell line and Cdk5 localizes to filopodia and vinculin-rich regions of cell-matrix contact in lamellopodia. When exposed to a 46(o)C heat shock, U373 cells change shape, lose cell-matrix contacts and show increased levels of apoptosis. To test whether Cdk5 activation might play a role in these events, U373 cells were stably transfected with histidine-tagged or green fluorescent protein-tagged constructs of Cdk5 or a dominant negative mutation, Cdk5T33. Under normal growth conditions, growth characteristics of the stably transfected lines were indistinguishable from untransfected U373 cells and Cdk5 localization was not changed. However, when subjected to heat shock, cells stably transfected with Cdk5-T33 remained flattened, showed little loss of cell-matrix adhesion, and exhibited significantly lower levels of apoptosis. In contrast, cells that overexpressed wild-type Cdk5 showed morphological changes similar to those seen in untransfected U373 cells in response to heat shock and had significantly higher levels of apoptosis. Heat-shocked cells showed changes in p35 mobility and stability of the Cdk5/p35 complex consistent with endogenous Cdk5 activity. Together these findings suggest that endogenous Cdk5 activity may play a key role in regulating morphology, attachment, and apoptosis in U373 cells, and raise the possibility that Cdk5 may be a general regulator of cytoskeletal organization and cell adhesion in both neuronal and non-neuronal cells.

Duke Scholars

Published In

J Cell Sci

DOI

ISSN

0021-9533

Publication Date

March 2001

Volume

114

Issue

Pt 6

Start / End Page

1145 / 1153

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Recombinant Fusion Proteins
  • Nerve Tissue Proteins
  • Humans
  • Heat-Shock Response
  • Developmental Biology
  • Cytoskeleton
  • Cyclin-Dependent Kinases
  • Cyclin-Dependent Kinase 5
  • Cell Fractionation
 

Citation

APA
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ICMJE
MLA
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Gao, C., Negash, S., Wang, H. S., Ledee, D., Guo, H., Russell, P., & Zelenka, P. (2001). Cdk5 mediates changes in morphology and promotes apoptosis of astrocytoma cells in response to heat shock. J Cell Sci, 114(Pt 6), 1145–1153. https://doi.org/10.1242/jcs.114.6.1145
Gao, C., S. Negash, H. S. Wang, D. Ledee, H. Guo, P. Russell, and P. Zelenka. “Cdk5 mediates changes in morphology and promotes apoptosis of astrocytoma cells in response to heat shock.J Cell Sci 114, no. Pt 6 (March 2001): 1145–53. https://doi.org/10.1242/jcs.114.6.1145.
Gao C, Negash S, Wang HS, Ledee D, Guo H, Russell P, et al. Cdk5 mediates changes in morphology and promotes apoptosis of astrocytoma cells in response to heat shock. J Cell Sci. 2001 Mar;114(Pt 6):1145–53.
Gao, C., et al. “Cdk5 mediates changes in morphology and promotes apoptosis of astrocytoma cells in response to heat shock.J Cell Sci, vol. 114, no. Pt 6, Mar. 2001, pp. 1145–53. Pubmed, doi:10.1242/jcs.114.6.1145.
Gao C, Negash S, Wang HS, Ledee D, Guo H, Russell P, Zelenka P. Cdk5 mediates changes in morphology and promotes apoptosis of astrocytoma cells in response to heat shock. J Cell Sci. 2001 Mar;114(Pt 6):1145–1153.
Journal cover image

Published In

J Cell Sci

DOI

ISSN

0021-9533

Publication Date

March 2001

Volume

114

Issue

Pt 6

Start / End Page

1145 / 1153

Location

England

Related Subject Headings

  • Tumor Cells, Cultured
  • Recombinant Fusion Proteins
  • Nerve Tissue Proteins
  • Humans
  • Heat-Shock Response
  • Developmental Biology
  • Cytoskeleton
  • Cyclin-Dependent Kinases
  • Cyclin-Dependent Kinase 5
  • Cell Fractionation