E2F Repression by C/EBPα Is Required for Adipogenesis and Granulopoiesis In Vivo

Porse, Bo; Pedersen, Thomas Åskov; Xu, Xiufeng; Lindberg, Bo G.; Wewer, Ulla M.; Friis‐Hansen, Lennart; Nerlov, Claus

doi:10.1016/s0092-8674(01)00516-5

Cited by 292 publications

(378 citation statements)

References 38 publications

Supporting

Mentioning

351

Contrasting

Order By: Relevance

“…The C/EBPαp30, compared with the full-length C/ EBPαp42, lacks the N-terminal 117 amino acids, which is required by adipocyte differentiation, granulopoiesis [12,22] and C/EBPα-Rb, C/EBPα-p21 interactions [8][9][10]. In liver cells, the expression ratio of C/EBPαp42 vs C/EBPαp30 is related to hepatocyte development [23].…”

Section: C/ebpαp30 Is More Than a Negative Regulator Of C/ Ebpαp42mentioning

confidence: 99%

See 1 more Smart Citation

C/EBPαp30 plays transcriptional regulatory roles distinct from C/EBPαp42

et al. 2007

View full text Add to dashboard Cite

CCAAT/enhancer binding protein α (C/EBPα) is a transcriptional regulatory factor that inhibits cell proliferation, and alternative translational initiation produces two polypeptides, C/EBPαp30 and C/EBPαp42. By expression profiling, it was revealed that C/EBPαp30 specifically inhibited a unique set of genes, including MPP11, p84N5 and SMYD2, which were not affected by C/EBPαp42 in both QSG-7701 hepatocyte cell line and QGY-7703 hepatoma cells. Semiquantitative RT-PCR analysis independently confirmed these results. Chromatin immunoprecipitation assay showed that C/EBPαp30 bound to the promoters of these genes more strongly than C/EBPαp42. In clinical hepatoma samples in which C/EBPα was downregulated, all three genes specifically inhibited by C/EBPαp30 were upregulated. However, repression of MPP11, p84N5 and SMYD2 genes might not be directly involved in C/EBPαp30-mediated growth inhibition. Our data suggest that C/EBPαp30 regulates a unique set of target genes and is more than a dominant-negative regulator of C/EBPαp42.

show abstract

Section: C/ebpαp30 Is More Than a Negative Regulator Of C/ Ebpαp42mentioning

confidence: 99%

“…It initiates growth arrest by stabilizing p21, and by disrupting E2F transcriptional complexes during the G1 phase of the cell cycle [7][8][9][10][11][12]. It was suggested that C/EBPα might be a tumor suppressor gene.…”

Section: Introductionmentioning

confidence: 99%

C/EBPαp30 plays transcriptional regulatory roles distinct from C/EBPαp42

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Potential antagonistic protein interactions leading to a block in C/EBPa function in AML have been well implicated in recent findings (Pabst et al, 2001a;Vangala et al, 2003;Zheng et al, 2004). Interestingly, C/EBPa also functions via direct proteinprotein interactions in normal stem cell development (Behre et al, 2002a;D'Alo et al, 2003;Muller et al, 2004); PU.1 and c-Jun inactivation (Rangatia et al, 2002;Reddy et al, 2002), E2F repression (Porse et al, 2001), and cdk2 and cdk4 inhibition (Wang et al, 2001) by C/EBPa are all accompanied by direct protein-protein interactions. Moreover, different protein partners of C/EBPa in young and old mice livers itself demonstrate the importance of protein-protein interactions during ageing (Iakova et al, 2003).…”

Section: Introductionmentioning

confidence: 97%

Proteomic identification of C/EBP-DBD multiprotein complex: JNK1 activates stem cell regulator C/EBPα by inhibiting its ubiquitination

et al. 2006

View full text Add to dashboard Cite

Functional inactivation of transcription factors in hematopoietic stem cell development is involved in the pathogenesis of acute myeloid leukemia (AML). Stem cell regulator C/enhancer binding protein (EBP)a is among such transcription factors known to be inactive in AML. This is either due to mutations or inhibition by protein-protein interactions. Here, we applied a mass spectrometry-based proteomic approach to systematically identify putative co-activator proteins interacting with the DNA-binding domain (DBD) of C/EBP transcription factors. In our proteomic screen, we identified c-Jun N-terminal kinase (JNK) 1 among others such as PAK6, MADP-1, calmodulin-like skin proteins and ZNF45 as proteins interacting with DBD of C/EBPs from nuclear extract of myelomonocytic U937 cells. We show that kinase JNK1 physically interacts with DBD of C/EBPa in vitro and in vivo. Furthermore, we show that active JNK1 inhibits ubiquitination of C/EBPa possibly by phosphorylating in its DBD. Consequently, JNK1 prolongs C/EBPa protein half-life leading to its enhanced transactivation and DNA-binding capacity. In certain AML patients, however, the JNK1 mRNA expression and its kinase activity is decreased which suggests a possible reason for C/EBPa inactivation in AML. Thus, we report the first proteomic screen of C/EBP-interacting proteins, which identifies JNK1 as positive regulator of C/EBPa.

show abstract

“…C/EBPa expression is associated with increased expression of p21 cell cycle inhibitory protein (16), cell cycle arrest after viral infection (17), and terminal differentiation (18). Loss-of-function mutations in C/EBPa are pro-proliferative and have been reported in acute myeloblastic leukemia (19).…”

Section: Discussionmentioning

confidence: 99%

A Nonclassic CCAAT Enhancer Element Binding Protein Binding Site Contributes to α-Methylacyl-CoA Racemase Expression in Prostate Cancer

Zha¹,

Isaacs²

2005

Molecular Cancer Research

View full text Add to dashboard Cite

A A A-Methylacyl-CoA racemase (AMACR), an enzyme involved in branched-chain fatty acid B B B-oxidation that is normally expressed at high levels in human liver, is specifically and consistently overexpressed at both mRNA and protein levels in human prostate cancer and potentially other cancer types. To characterize the mechanisms underlying transcriptional regulation of AMACR at the genetic and epigenetic levels, we performed a series of methylation and reporter assays in prostate cancer tissues and cell lines. The results ruled out altered methylation patterns as the cause of overexpression in prostate cancer cells. However, promoter deletion analysis identified an 8-bp nonclassic CCAAT enhancer element located f f80 bp upstream of the transcriptional initiation site that is responsible for AMACR expression in both prostate cancer cell lines and cell lines of liver origin. Deletion or mutation of this element completely abolished AMACR promoter activity. Ectopic expression of CCAAT/enhancer binding protein B B B increased luciferase activity driven by a wild-type AMACR promoter sequence but not by the sequence in which the putative CCAAT/enhancer binding protein binding element had been mutated. These results implicate a nonclassic CCAAT enhancer element in the AMACR gene promoter as playing a critical role in the regulation of AMACR gene expression. (Mol Cancer Res 2005;3(2):110 -8)

show abstract

E2F Repression by C/EBPα Is Required for Adipogenesis and Granulopoiesis In Vivo

Cited by 292 publications

References 38 publications

C/EBPαp30 plays transcriptional regulatory roles distinct from C/EBPαp42

C/EBPαp30 plays transcriptional regulatory roles distinct from C/EBPαp42

Proteomic identification of C/EBP-DBD multiprotein complex: JNK1 activates stem cell regulator C/EBPα by inhibiting its ubiquitination

A Nonclassic CCAAT Enhancer Element Binding Protein Binding Site Contributes to α-Methylacyl-CoA Racemase Expression in Prostate Cancer

Contact Info

Product

Resources

About