| Dephosphorylation of Rb (Thr-821) in response to cell stress. | |
| | |
MedLine Citation:
|
PMID: 16764854 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The retinoblastoma tumor suppressor Rb is regulated by reversible phosphorylation that is dependent upon cyclin-dependent kinase (CDK) and protein phosphatase type 1 (PP1) activity in replicating cells. Hyperphosphorylated Rb allows cells to proliferate, whereas the hypophosphorylated isoform of Rb inhibits proliferation. Of the many phosphorylation sites of Rb, there is functional information available for a very few. In this report, we show that threonine-821 (Thr-821) of Rb is dephosphorylated earlier than other phosphorylation sites when cells are grown under hypoxic conditions which leads to Rb activation and G(1) arrest. This finding is interesting because Thr-821 of Rb remains phosphorylated throughout the cell division cycle in replicating cells. We hypothesized that the phosphorylation state of Thr-821 of Rb may depend on cellular stress. We report in this study that, when nontransformed CV1 epithelial cells and Hs578T breast cancer cells are treated with the chemotherapeutic agent cytosine arabinoside (Ara-C), Thr-821 of Rb is rapidly dephosphorylated concomitant with dissociation of the PP1 regulatory subunit PNUTS (phosphatase nuclear targeting subunit) from PP1 enzyme. These data are consistent with the concept that differential regulation of Rb-directed phosphatase activity exists when cells are progressing through the cell cycle compared to that observed when cells are under stress. |
| | |
Authors:
|
Nancy A Krucher; Ethel Rubin; Vivienne C Tedesco; Michael H Roberts; Tara C Sherry; Gabriel De Leon |
Related Documents
:
|
18370874 - Cyclin-dependent kinase inhibitor roscovitine induces cell cycle arrest and apoptosis i... 18413744 - Micrornas 221 and 222 bypass quiescence and compromise cell survival. 9819434 - Raf-1 physically interacts with rb and regulates its function: a link between mitogenic... 15332324 - Inducible expression of p57kip2 inhibits glioma cell motility and invasion. 15114264 - Immunohistochemical analysis of the interstitial mast cells in acute rejection of human... 22670904 - Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2006-05-10 |
Journal Detail:
|
Title: Experimental cell research Volume: 312 ISSN: 0014-4827 ISO Abbreviation: Exp. Cell Res. Publication Date: 2006 Sep |
Date Detail:
|
Created Date: 2006-08-25 Completed Date: 2006-10-19 Revised Date: 2007-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 0373226 Medline TA: Exp Cell Res Country: United States |
Other Details:
|
Languages: eng Pagination: 2757-63 Citation Subset: IM |
Affiliation:
|
Department of Biology and Health Sciences, Pace University, 109 Dyson Hall, 861 Bedford Road, Pleasantville, NY 10570, USA. nkrucher@pace.edu |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Antimetabolites, Antineoplastic
/
metabolism,
pharmacology Cell Cycle / drug effects Cell Hypoxia Cytarabine / metabolism, pharmacology DNA-Binding Proteins / metabolism Epithelial Cells / cytology, metabolism Female Humans Nuclear Proteins / metabolism Phosphoprotein Phosphatases / metabolism Phosphorylation / drug effects Protein Subunits / metabolism RNA-Binding Proteins / metabolism Retinoblastoma Protein / metabolism* Threonine / metabolism Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
|
R15 CA 88803-01A2/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Antimetabolites, Antineoplastic; 0/DNA-Binding Proteins; 0/Nuclear Proteins; 0/PPP1R10 protein, human; 0/Protein Subunits; 0/RNA-Binding Proteins; 0/Retinoblastoma Protein; 147-94-4/Cytarabine; 72-19-5/Threonine; EC 3.1.3.16/Phosphoprotein Phosphatases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: EVI5 protein associates with the INCENP-aurora B kinase-survivin chromosomal passenger complex and i...
Next Document: Structural components of the synaptonemal complex, SYCP1 and SYCP3, in the medaka fish Oryzias latip...