Identification of Xenopus cyclin-dependent kinase inhibitors, p16Xic2 and p17Xic3.
The Cip/Kip family of mammalian cyclin-dependent kinase (cdk) inhibitors plays important roles in development, particularly in cell fate determination and differentiation, in addition to their function of blocking cell cycle progression. We have identified two novel members of the Kip/Cip cdk inhibitor family, p16Xic2 and p17Xic3, from Xenopus laevis. Sequence analysis revealed that p16Xic2 and p17Xic3 are orthologues of mammalian p21Cip1 and p27Kip1, respectively. Overexpression of these inhibitors results in cell cycle arrest by inhibition of cdk2 activity. Interestingly, the expression of these inhibitors is highly developmentally regulated. p16Xic2 is highly expressed in differentiating somite, tail bud, lens, and cement gland, while p17Xic3 is expressed in the central nervous system. In a retinal cell fate determination assay, both p16Xic2 and p17Xic3 have an activity that influences cell fate determination. These observations suggest that p16Xic2 and p17Xic3 might be involved in cell fate determination in a tissue-specific manner by coordinating proliferation and differentiation as observed with p27Xic1.
Daniels
Maki
M
Department of Oncology, The Hutchison/MRC Research Centre, University of Cambridge, Hills Road, Cambridge, CB2 2XZ, UK.
Dhokia
Vishal
V
Richard-Parpaillon
Laurent
L
Ohnuma
Shin-Ichi
S
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003001:Cloning, Molecular; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D008297:Male; D008845:Microinjections; D008969:Molecular Sequence Data; D010802:Phylogeny; D012333:RNA, Messenger / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D029867:Xenopus Proteins / Q000235:genetics*; D014982:Xenopus laevis / Q000196:embryology / Q000235:genetics*
C494524:CDKN1A protein, Xenopus; D002352:Carrier Proteins; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D018076:DNA, Complementary; D012333:RNA, Messenger; D029867:Xenopus Proteins; C494525:p17Xic3 protein, Xenopus; D018844:Cyclin-Dependent Kinases