p27Kip1 and p130 cooperate to regulate hematopoietic cell proliferation in vivo

Inês Soeiro, Azim Mohamedali, Hanna M. Romanska, Nicholas C. Lea, Emma S. Child, Janet Glassford, Stephen J. Orr, Claudia Roberts, Kikkeri N. Naresh, El Nasir Lalani, David J. Mann, Roger J. Watson, N. Shaun B. Thomas, Eric W.F. Lam

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


To investigate the potential functional cooperation between p27 Kip1 and p130 in vivo, we generated mice deficient for both p27 Kip1 and p130. In p27Kip1-/-;o130-/- 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 pl30 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 p27 Kip1-/-; 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.

Original languageEnglish
Pages (from-to)6170-6184
Number of pages15
JournalMolecular and Cellular Biology
Issue number16
Publication statusPublished - Aug 2006
Externally publishedYes


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