Control of thymocyte proliferation and thymus organ size by CDK inhibitors P18INK4c and P27KIP1

Grigoriy I. Kovalev, Tamara D. Simon, V. McNeil Coffield, Yue Xiong, David S. Franklin, Lishan Su

Research output: Contribution to journalArticlepeer-review

Abstract

The cyclin-dependent kinase (CDK) inhibitors p18INK4c and p27KIP1 are both highly expressed in the thymus and loss of p18 or p27 results in enlarged thymus in mice. To investigate the regulation of thymopoiesis by these two CDK inhibitors, we analyzed the thymocytes and thymus organs of p18-/-, p27-/+, and p18-/-/p27-/- mutant mice. The p18-/- or p27-/- thymus organ was larger than the wild-type thymus, and p18-/-/p27-/- thymus organ was further enlarged than either p18-/- or p27-/- thymus. The hematopoietic progenitor cells in the bone marrow and the major thymocyte subpopulations including pro-T and pre-T precursors remained normal in proportion and cell size. The sensitivity of thymocytes to dexamethasone, γ-radiation, and CD3/CD28 stimulation was not altered in single or double knockout (KO) mice. However, significantly increased numbers of cycling thymocytes were detected in either p18-/- or p27-/- mice, and an even higher percent of cycling thymocytes were detected in p18-/-/p27-/- mice. We found that p18 was preferentially associated with CDK6 in thymocytes and absence of p27 did not change this association, while p27 preferentially bound CDK4 and CDK2 and their association was not changed in the absence of p18. We conclude that by regulating different CDKs, p18 and p27 independently and cooperatively control thymocyte proliferation and thymus organ size.

Original languageEnglish
Pages (from-to)97-108
Number of pages12
JournalJournal of Stem Cells
Volume1
Issue number2
Publication statusPublished - 2006
Externally publishedYes

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