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First published online April 22, 2009

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Boning up on cyclin D1

Parathyroid hormone-related protein (PTHrP) is a growth factor that maintains chondrocytes in a proliferative state and prevents premature hypertrophy during bone and cartilage formation. But what are the mechanisms that underlie PTHrP-mediated regulation of chondrocyte growth? Previous work has shown that PTHrP induces the expression of cyclin D1 (which promotes the G1-to-S transition of the cell cycle), and that cyclin D1 induces the degradation of the transcription factor Runx2 (which is known to contribute to chondrocyte maturation). Now, Di Chen and colleagues (p. 1382) tie these findings together with new data by showing that PTHrP induces cyclin-D1-dependent phosphorylation and ubiquitin-dependent proteasomal degradation of both Runx2 and Runx3. They find that, similar to Runx2, Runx3 contains a crucial serine residue that is phosphorylated by cyclin D1, thereby targeting Runx3 for degradation. Compared with wild-type mice, chondrocytes from mice lacking cyclin D1 have increased expression of Runx2 and Runx3; in line with the capacity of these transcription factors to promote chondrocyte maturation, cyclin-D1-deficient mice show an accelerated rate of chondrocyte differentiation. The authors conclude that these findings represent a newly defined pathway that explains how PTHrP prevents premature hypertrophy in chondrocytes.

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PTHrP prevents chondrocyte premature hypertrophy by inducing cyclin-D1-dependent Runx2 and Runx3 phosphorylation, ubiquitylation and proteasomal degradation

Ming Zhang, Rong Xie, Wei Hou, Baoli Wang, Run Shen, Xiumei Wang, Qing Wang, Tianhui Zhu, Jennifer H. Jonason, and Di Chen
JCS 2009 122: 1382-1389. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?