The cdc-2-related kinase, PISSLRE, is essential for cell growth and acts in G2 phase of the cell cycle.
Mammalian cell cycle progression is regulated by several protein kinases that are activated by cyclically expressed proteins called cyclins. These cyclin-dependent kinases, the prototype of which is the cdc2 mitosis-promoting kinase, are known to phosphorylate substrates the modified status of which is critical for the cell to progress into sequential phases of the cycle. Recently, a new cdc2-related protein kinase has been discovered. PISSLRE, named with respect to its homology to the cdc2 PSTAIRE amino acid domain. Here we report that by using both antisense and dominant-negative mutant constructs of PISSLRE when overexpressed in U2OS cells, a growth suppression is found. Furthermore, the dominant negative forms of PISSLRE halt cell cycle progression in G2-M. Therefore, PISSLRE is essential for cellular proliferation, and its effect is exerted in G2-M. This describes the first evidence since cdc2 of a cdc2-related kinase acting through G2-M.
Li
S
S
Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
MacLachlan
T K
TK
De Luca
A
A
Claudio
P P
PP
Condorelli
G
G
Giordano
A
A
D000595:Amino Acid Sequence; D002455:Cell Division; D018844:Cyclin-Dependent Kinases; D004261:DNA Replication; D016195:G2 Phase; D006801:Humans; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000502:physiology*; D014407:Tumor Cells, Cultured
D011494:Protein Kinases; C501013:CDK10 protein, human; D018844:Cyclin-Dependent Kinases