ArticleMolecular and cellular biology2006
Cyclin D3 maintains growth-inhibitory activity of C/EBPalpha by stabilizing C/EBPalpha-cdk2 and C/EBPalpha-Brm complexes.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 73 citations in OpenAlex.
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- The miRNA Contribution in Adipocyte Maturation.Non-coding RNA · 2024Article
- Effect of resistance training on satellite cells in old mice - a transcriptome study : implications for sarcopenia.Bone & joint research · 2022Article
- miR-138-5p suppresses glioblastoma cell viability and leads to cell cycle arrest by targeting cyclin D3.Oncology letters · 2020Article
- Long non-coding RNA slincRAD functions in methylation regulation during the early stage of mouse adipogenesis.RNA biology · 2019Article
- C/EBPα mediates the growth inhibitory effect of progestins on breast cancer cells.The EMBO journal · 2019Article
- Association of the invasiveness of colon cancer with the expression of C/EBPα.Oncology letters · 2019Article
- Liver regeneration in aged mice: new insights.Aging · 2018Review
- Elimination of Age-Associated Hepatic Steatosis and Correction of Aging Phenotype by Inhibition of cdk4-C/EBPα-p300 Axis.Cell reports · 2018Article
- C/EBPα-dependent preneoplastic tumor foci are the origin of hepatocellular carcinoma and aggressive pediatric liver cancer.Hepatology (Baltimore, Md.) · 2018Article
- Role of cell cycle regulators in adipose tissue and whole body energy homeostasis.Cellular and molecular life sciences : CMLS · 2018Review
- Ghrelin deletion protects against age-associated hepatic steatosis by downregulating the C/EBPα-p300/DGAT1 pathway.Aging cell · 2018Article
- Review
- Article
- IL-17 promotes keratinocyte proliferation via the downregulation of C/EBPα.Experimental and therapeutic medicine · 2016Article
- Improved adipogenic in vitro differentiation: comparison of different adipogenic cell culture media on human fat and bone stroma cells for fat tissue engineering.Anatomy & cell biology · 2015Article
- Article
- Androgen Receptor-Mediated Growth Suppression of HPr-1AR and PC3-Lenti-AR Prostate Epithelial Cells.PloS one · 2015Article
- Increased expression of enzymes of triglyceride synthesis is essential for the development of hepatic steatosis.Cell reports · 2013Article
- CCAAT/enhancer binding protein-α regulates the protease/antiprotease balance required for bronchiolar epithelium regeneration.American journal of respiratory cell and molecular biology · 2012Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
C/EBPalpha arrests proliferation of young livers by inhibition of cdk2. In old mice, C/EBPalpha inhibits growth by repression of E2F-dependent promoters through the C/EBPalpha-Brm complex. In this paper, we show that cyclin D3-cdk4/cdk6 supports the ability of C/EBPalpha to inhibit liver proliferation in both age groups. Although cyclin D3-cdk4/cdk6 kinases are involved in the promotion of growth, they are expressed in terminally differentiated cells, suggesting that they have additional functions in these settings. We demonstrate that C/EBPalpha represents a target for phosphorylation by cyclin D3-cdk4/cdk6 complexes in differentiated liver cells and in differentiated adipocytes. Cyclin D3-cdk4/cdk6 specifically phosphorylate C/EBPalpha at Ser193 in vitro and in the liver and support growth-inhibitory C/EBPalpha-cdk2 and C/EBPalpha-Brm complexes. We found that cyclin D3 is increased in old livers and activates cdk4/cdk6, resulting in stabilization of the C/EBPalpha-Brm complex. Old livers fail to reduce the activity of cyclin D3-cdk4/cdk6 after partial hepatectomy, leading to high levels of C/EBPalpha-Brm complexes after partial hepatectomy, which correlate with weak proliferation. We examined the role of cyclin D3 in the stabilization of C/EBPalpha-cdk2 and C/EBPalpha-Brm by using 3T3-L1 differentiated cells. In these cells, cyclin D3 is increased during differentiation and phosphorylates C/EBPalpha at Ser193, leading to the formation of growth-inhibitory C/EBPalpha-cdk2 and C/EBPalpha-Brm complexes. The inhibition of cyclin D3 blocks the formation of these complexes. Thus, these studies provide a new function of cyclin D3, which is to support the growth-inhibitory activity of C/EBPalpha.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.