Evidence for coordinated interaction of cyclin D3 with p21 and cdk6 in directing the development of uterine stromal cell decidualization and polyploidy during implantation.
Uterine decidualization, characterized by stromal cell proliferation, and differentiation into specialized type of cells (decidual cells) with polyploidy, during implantation is critical to the pregnancy establishment in mice. The mechanisms by which the cell cycle events govern these processes are poorly understood. The cell cycle is tightly regulated at two particular checkpoints, G1-S and G2-M phases. Normal operation of these phases involves a complex interplay of cyclins, cyclin-dependent kinases (cdks) and cdk inhibitors (CKIs). We previously observed that upregulation of uterine cyclin D3 at the implantation site is tightly associated with decidualization in mice. To better understand the role of cyclin D3 in this process, we examined cell-specific expression and associated interactions of several cell cycle regulators (cyclins, cdks and CKIs) specific to different phases of the cell cycle during decidualization in mice. Among the various cell cycle molecules examined, coordinate expression and functional association of cyclin D3 with cdk4 suggest a role for proliferation and, that of cyclin D3 with p21 and cdk6 is consistent with the development of polyploidy during stromal cell decidualization.
Tan
Jian
J
Department of Obstetrics and Gynecology, MRRC 37/3004, Ralph L. Smith Research Center, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160-7338, USA.
Raja
Shefali
S
Davis
Marilyn K
MK
Tawfik
Ossama
O
Dey
Sudhansu K
SK
Das
Sanjoy K
SK
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D056743:Cyclin D3; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism*; D003656:Decidua / Q000502:physiology; D010064:Embryo Implantation / Q000502:physiology*; D005260:Female; D016193:G1 Phase / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011123:Polyploidy; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D017154:Stromal Cells / Q000378:metabolism; D014599:Uterus / Q000166:cytology* / Q000502:physiology
C534697:Ccnd3 protein, mouse; C493957:Cdkn1a protein, mouse; D056743:Cyclin D3; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011518:Proto-Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; C495902:Cdk4 protein, mouse; C495912:Cdk6 protein, mouse; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases