Document Detail


The involvement of two cdc2-related kinases (CRKs) in Trypanosoma brucei cell cycle regulation and the distinctive stage-specific phenotypes caused by CRK3 depletion.
MedLine Citation:
PMID:  15010459     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cyclin-dependent protein kinases are among the key regulators of eukaryotic cell cycle progression. Potential functions of the five cdc2-related kinases (CRK) in Trypanosoma brucei were analyzed using the RNA interference (RNA(i)) technique. In both the procyclic and bloodstream forms of T. brucei, CRK1 is apparently involved in controlling the G(1)/S transition, whereas CRK3 plays an important role in catalyzing cells across the G(2)/M junction. A knockdown of CRK1 caused accumulation of cells in the G(1) phase without apparent phenotypic change, whereas depletion of CRK3 enriched cells of both forms in the G(2)/M phase. However, two distinctive phenotypes were observed between the CRK3-deficient procyclic and bloodstream forms. The procyclic form has a majority of the cells containing a single enlarged nucleus plus one kinetoplast. There is also an enhanced population of anucleated cells, each containing a single kinetoplast known as the zoids (0N1K). The CRK3-depleted bloodstream form has an increased number of one nucleus-two kinetoplast cells (1N2K) and a small population containing aggregated multiple nuclei and multiple kinetoplasts. Apparently, these two forms have different mechanisms in cell cycle regulation. Although the procyclic form can be driven into cytokinesis and cell division by kinetoplast segregation without a completed mitosis, the bloodstream form cannot enter cytokinesis under the same condition. Instead, it keeps going through another G(1) phase and enters a new S phase resulting in an aggregate of multiple nuclei and multiple kinetoplasts in an undivided cell. The different leakiness in cell cycle regulation between two stage-specific forms of an organism provides an interesting and useful model for further understanding the evolution of cell cycle control among the eukaryotes.
Authors:
Xiaoming Tu; Ching C Wang
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2004-03-08
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  279     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-05-04     Completed Date:  2004-06-15     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  20519-28     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutical Chemistry, University of California-San Francisco, San Francisco, CA 94143-2280, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antimetabolites, Antineoplastic / pharmacology
CDC2 Protein Kinase / physiology*
Cell Cycle
Cell Division
Cell Nucleus / metabolism
Cell Separation
Coloring Agents / pharmacology
DNA, Complementary / metabolism
Flow Cytometry
G1 Phase
G2 Phase
Mitosis
Phenotype
Protozoan Proteins / physiology*
RNA Interference
Reverse Transcriptase Polymerase Chain Reaction
S Phase
Time Factors
Transfection
Trypanosoma brucei brucei / enzymology*
Grant Support
ID/Acronym/Agency:
R01 AI 2178/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antimetabolites, Antineoplastic; 0/Coloring Agents; 0/DNA, Complementary; 0/Protozoan Proteins; EC 2.7.1.37/crk1 protein,Trypanosoma brucei; EC 2.7.10.-/CRK3 kinase, protozoa; EC 2.7.11.22/CDC2 Protein Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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