| pubmed-article:16467204 | rdf:type | pubmed:Citation | lld:pubmed |
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| pubmed-article:16467204 | lifeskim:mentions | umls-concept:C0014819 | lld:lifeskim |
| pubmed-article:16467204 | lifeskim:mentions | umls-concept:C0007586 | lld:lifeskim |
| pubmed-article:16467204 | lifeskim:mentions | umls-concept:C0596290 | lld:lifeskim |
| pubmed-article:16467204 | lifeskim:mentions | umls-concept:C1420433 | lld:lifeskim |
| pubmed-article:16467204 | lifeskim:mentions | umls-concept:C1332812 | lld:lifeskim |
| pubmed-article:16467204 | lifeskim:mentions | umls-concept:C0699900 | lld:lifeskim |
| pubmed-article:16467204 | lifeskim:mentions | umls-concept:C1424666 | lld:lifeskim |
| pubmed-article:16467204 | lifeskim:mentions | umls-concept:C1415887 | lld:lifeskim |
| pubmed-article:16467204 | lifeskim:mentions | umls-concept:C1419040 | lld:lifeskim |
| pubmed-article:16467204 | lifeskim:mentions | umls-concept:C0598086 | lld:lifeskim |
| pubmed-article:16467204 | lifeskim:mentions | umls-concept:C0598388 | lld:lifeskim |
| pubmed-article:16467204 | lifeskim:mentions | umls-concept:C0243125 | lld:lifeskim |
| pubmed-article:16467204 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:16467204 | lifeskim:mentions | umls-concept:C1511938 | lld:lifeskim |
| pubmed-article:16467204 | lifeskim:mentions | umls-concept:C1521840 | lld:lifeskim |
| pubmed-article:16467204 | lifeskim:mentions | umls-concept:C0337094 | lld:lifeskim |
| pubmed-article:16467204 | pubmed:issue | 11 | lld:pubmed |
| pubmed-article:16467204 | pubmed:dateCreated | 2006-5-23 | lld:pubmed |
| pubmed-article:16467204 | pubmed:abstractText | As erythroid progenitors differentiate into precursors and finally mature red blood cells, lineage-specific genes are induced, and proliferation declines until cell cycle exit. Cul4A encodes a core subunit of a ubiquitin ligase that targets proteins for ubiquitin-mediated degradation, and Cul4A-haploinsufficient mice display hematopoietic dysregulation with fewer multipotential and erythroid-committed progenitors. In this study, stress induced by 5-fluorouracil or phenylhydrazine revealed a delay in the recovery of erythroid progenitors, early precursors, and normal hematocrits in Cul4A(+/-) mice. Conversely, overexpression of Cul4A in a growth factor-dependent, proerythroblast cell line increased proliferation and the proportion of cells in S phase. When these proerythroblasts were induced to terminally differentiate, endogenous Cul4A protein expression declined 3.6-fold. Its enforced expression interfered with erythrocyte maturation and cell cycle exit and, instead, promoted proliferation. Furthermore, p27 normally accumulates during erythroid terminal differentiation, but Cul4A-enforced expression destabilized p27 and attenuated its accumulation. Cul4A and p27 proteins coimmunoprecipitate, indicating that a Cul4A ubiquitin ligase targets p27 for degradation. These findings indicate that a Cul4A ubiquitin ligase positively regulates proliferation by targeting p27 for degradation and that Cul4A down-regulation during terminal erythroid differentiation allows p27 to accumulate and signal cell cycle exit. | lld:pubmed |
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| pubmed-article:16467204 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16467204 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16467204 | pubmed:citationSubset | AIM | lld:pubmed |
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| pubmed-article:16467204 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16467204 | pubmed:month | Jun | lld:pubmed |
| pubmed-article:16467204 | pubmed:issn | 0006-4971 | lld:pubmed |
| pubmed-article:16467204 | pubmed:author | pubmed-author:LEER CRC | lld:pubmed |
| pubmed-article:16467204 | pubmed:author | pubmed-author:KapurReubenR | lld:pubmed |
| pubmed-article:16467204 | pubmed:author | pubmed-author:LiBinghuiB | lld:pubmed |
| pubmed-article:16467204 | pubmed:author | pubmed-author:ChunKristin... | lld:pubmed |
| pubmed-article:16467204 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:16467204 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:16467204 | pubmed:volume | 107 | lld:pubmed |
| pubmed-article:16467204 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:16467204 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:16467204 | pubmed:pagination | 4291-9 | lld:pubmed |
| pubmed-article:16467204 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
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