| First Author | Soeiro I | Year | 2006 |
| Journal | Mol Cell Biol | Volume | 26 |
| Issue | 16 | Pages | 6170-84 |
| PubMed ID | 16880527 | Mgi Jnum | J:111578 |
| Mgi Id | MGI:3654421 | Doi | 10.1128/MCB.02182-05 |
| Citation | Soeiro I, et al. (2006) p27Kip1 and p130 cooperate to regulate hematopoietic cell proliferation in vivo. Mol Cell Biol 26(16):6170-84 |
| abstractText | To investigate the potential functional cooperation between p27Kip1 and p130 in vivo, we generated mice deficient for both p27Kip1 and p130. In p27Kip1-/-; p130-/- mice, the cellularity of the spleens but not the thymi is significantly increased compared with that of their p27Kip1-/- counterparts, affecting the lymphoid, erythroid, and myeloid compartments. In vivo cell proliferation is significantly augmented in the B and T cells, monocytes, macrophages, and erythroid progenitors in the spleens of p27Kip1-/-; p130-/- animals. Immunoprecipitation and immunodepletion studies indicate that p130 can compensate for the absence of p27Kip1 in binding to and repressing CDK2 and is the predominant CDK-inhibitor associated with the inactive CDK2 in the p27Kip1-/- splenocytes. The finding that the p27Kip1-/-; p130-/- splenic B cells are hypersensitive to mitogenic stimulations in vitro lends support to the concept that the hyperproliferation of splenocytes is not a result of the influence of their microenvironment. In summary, our findings provide genetic and molecular evidence to show that p130 is a bona fide cyclin-dependent kinase inhibitor and cooperates with p27Kip1 to regulate hematopoietic cell proliferation in vivo. |
