Journal
NATURE IMMUNOLOGY
Volume 7, Issue 5, Pages 489-497Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni1324
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Funding
- NCI NIH HHS [R01CA105129] Funding Source: Medline
- NIGMS NIH HHS [R01GM52736] Funding Source: Medline
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During hematopoiesis, stem cell proliferation is dependent on expression of the D-type cyclins. However, little is known about how each cyclin D contributes to the development of specific hematopoietic lineages. Here, analysis of Ccnd1(-/-), Ccnd2(-/-), Ccnd3(-/-) and Ccnd2(-/-) Ccnd3(-/-) mice showed that cyclin D3 was uniquely required for the development of pre-B cells. Transcription of Ccnd3 was dependent on expression of the common gamma-chain. In contrast, expression of the pre-B cell receptor and activation of 'downstream' signaling pathways prevented proteasome-mediated degradation of cyclin D3. Cyclin D3 has a key function in B cell development by integrating cytokine and pre-B cell receptor-dependent signals to expand the pool of pre-B cells that have successfully rearranged immunoglobulin heavy chain.
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