Alternative splicing of human cyclin E.
Cyclin E is a regulatory subunit of the cdc2-related protein kinase cdk2, which is activated shortly before S-phase entry, thus defining it as a G1 cyclin. We report here the existence of a 43 kDa splice variant of human cyclin E, termed cyclin Es, which lacks 49 amino acids within the cyclin box compared to the known 48 kDa cyclin E. Cyclin Es is expressed at approximately 1/10 of the level of full-length cyclin E in several cell lines analysed. The two cyclin E forms differ functionally in that cyclin E, but not cyclin Es, is able to complex with cdk2, to activate the histone H1, pRb and p107 in vitro kinase activity of cdk2 and to rescue a triple CLN mutation in S. cerevisiae. Cyclin Es is the first splice variant of a cell cycle regulatory protein to be described. Our findings also indicate that the cyclin box in cyclin E mediates the interaction with cdk2.
Sewing
A
A
Institut für Molekularbiologie und Tumorforschung (IMT), Philipps-Universität Marburg, Germany.
Rönicke
V
V
Bürger
C
C
Funk
M
M
Müller
R
R
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D042846:CDC2-CDC28 Kinases; D002460:Cell Line; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics
D016213:Cyclins; D017931:DNA Primers; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases