p27Kip1 and p130 cooperate to regulate hematopoietic cell proliferation in vivo

I Soeiro, A Mohamedali, Hanna Romanska, NC Lea, ES Child, J Glassford, SJ Orr, Claudia Roberts, KN Naresh, El-Nasir Lalani, DJ Mann, RJ Watson, NS Thomas, EW Lam

Research output: Contribution to journalArticle

15 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)6170-6184
Number of pages15
JournalMolecular and Cellular Biology
Publication statusPublished - 15 Aug 2006


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