p205, A potential tumor suppressor, inhibits cell proliferation via multiple pathways of cell cycle regulation

Asefa, Benyam; Dermott, Jonathan M.; Kaldis, Philipp; Stefanisko, Karen; Garfinkel, David; Keller, Jonathan R.

doi:10.1016/j.febslet.2006.01.032

Cited by 30 publications

(22 citation statements)

References 38 publications

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“…Interferon activable protein (p205) is involved in both lymphoid and myeloid differentiation (Asefa et al, 2006). Our results suggest that p205 is involved in withdrawal from the cell cycle.…”

Section: Intermediate Differentiation Stagementioning

confidence: 72%

Proteomics-based investigation in C2C12 myoblast differentiation

Casadei¹,

Vallorani²,

Gioacchini³

et al. 2009

Eur J Histochem

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Skeletal muscle cell differentiation is a multistage process extensively studied over the years. Even if great improvements have been achieved in defining biological process underlying myogenesis, many molecular mechanisms need still to be clarified. To further highlight this process, we studied cells at undifferentiated, intermediate and highly differentiated stages, and we analyzed, for each condition, morphological and proteomic changes. We also identified the proteins that showed statistical significant changes by a ESI-Q-TOF mass spectrometer. This work provides further evidence of the involvement of particular proteins in skeletal muscle development. Furthermore, the high level of expression of many heat shock proteins, suggests a relationship between differentiation and cellular stress. Intriguingly, the discovery of myogenesis-correlated proteins, known to play a role in apoptosis, suggests a link between differentiation and this type of cell death.

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Section: Intermediate Differentiation Stagementioning

confidence: 72%

Proteomics-based investigation in C2C12 myoblast differentiation

Casadei¹,

Vallorani²,

Gioacchini³

et al. 2009

Eur J Histochem

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“…The antiproliferative activity of p204 has been attributed to the binding of p204 to pRb by its pRb binding LXCXE motifs (Gribaudo et al, 1999;Liu et al, 1999;Hertel et al, 2000). However, the antiproliferative activity of p204 does not always depend on pRb (Asefa et al, 2006) (Ding and Lengyel, unpublished data). Overexpression of p204 was found to delay the progression of cells from the G0/G1 phase to the S phase of the cell cycle (Lembo et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

p204 Protein Overcomes the Inhibition of Core Binding Factor α-1–mediated Osteogenic Differentiation by Id Helix-Loop-Helix Proteins

Luan

Yang

et al. 2008

MBoC

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Id proteins play important roles in osteogenic differentiation; however, the molecular mechanism remains unknown. In this study, we established that inhibitor of differentiation (Id) proteins, including Id1, Id2, and Id3, associate with core binding factor ␣-1 (Cbfa1) to cause diminished transcription of the alkaline phosphatase (ALP) and osteocalcin (OCL) gene, leading to less ALP activity and osteocalcin (OCL) production. Id acts by inhibiting the sequence-specific binding of Cbfa1 to DNA and by decreasing the expression of Cbfa1 in cells undergoing osteogenic differentiation. p204, an interferon-inducible protein that interacts with both Cbfa1 and Id2, overcame the Id2-mediated inhibition of Cbfa1-induced ALP activity and OCL production. We show that 1) p204 disturbed the binding of Id2 to Cbfa1 and enabled Cbfa1 to bind to the promoters of its target genes and 2) that p204 promoted the translocation from nucleus to the cytoplasm and accelerated the degradation of Id2 by ubiquitin-proteasome pathway during osteogenesis. Nucleus export signal (NES) of p204 is required for the p204-enhanced cytoplasmic translocation and degradation of Id2, because a p204 mutant lacking NES lost these activities. Together, Cbfa1, p204, and Id proteins form a regulatory circuit and act in concert to regulate osteoblast differentiation. INTRODUCTIONThe differentiation of uncommitted mesenchymal cells to osteoblasts is a fundamental process in embryonic development and bone repair. The bone morphogenetic proteins (BMPs) are important regulators of this process (Heldin et al., 1997;Miyazono et al., 2000). They function by binding cell surface receptors; signaling by Smad proteins; and activating bone-specific genes, including core binding factor ␣-1 (Cbfa1) (Ducy, 2000;Miyazono et al., 2001;Attisano and Wrana, 2002). This process is positively or negatively regulated by a variety of coactivators and corepressors (Ducy et al., 2000;Miyazono et al., 2001;Attisano and Wrana, 2002). Cbfa1, also known as Runx2, PeBP2␣A, Osf2, or AML3, is a member of the runt family of transcription factors. It is an essential transcription factor of osteoblast and bone formation (Ducy, 2000). During skeletal development, Cbfa1 is observed first in early mesenchymal condensations, and it is then principally expressed in osteoblasts . Cbfa1 Ϫ/Ϫ mice exhibit a complete lack of ossification, and they die immediately after birth (Komori et al., 1997). Cbfa1 maintains osteoblastic function by regulating the expression of several bone-specific genes such as osteopontin and osteocalcin and by controlling bone extracellular matrix deposition (Ducy, 2000). Mutations in Cbfa1 are found in 65-80% of individuals with cleidocranial dysplasia (CCD) (Lee et al., 1997;Mundlos and Olsen, 1997;Zhou et al., 1999). The molecular mechanisms underlying the pathogenesis of CCD are not completely defined. Some mutations of Cbfa1 abolish its DNA binding activity (Lee et al., 1997;Zhou et al., 1999) and others disturb the association of Cbfa1 to its binding partners, including Sma...

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“…The antiproliferative activity of p204 has been attributed to the binding of p204 to pRb by its pRb binding LXCXE motifs (24,26,27). However, the antiproliferative activity of p204 does not always depend on pRb (28). 3 Overexpression of p204 was found to delay the progression of cells from the G 0 /G 1 phase to the S phase of the cell cycle (29).…”

mentioning

confidence: 99%

The Retinoblastoma Protein Is an Essential Mediator of Osteogenesis That Links the p204 Protein to the Cbfa1 Transcription Factor Thereby Increasing Its Activity

Luan

et al. 2007

Journal of Biological Chemistry

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Bone formation requires the coordinated activity of numerous proteins including the transcription factor core-binding factor ␣1 (Cbfa1). Deregulation of Cbfa1 results in metabolic bone diseases including osteoporosis and osteopetrosis. The retinoblastoma protein (pRb) that is required for osteogenesis binds Cbfa1. We reported earlier that the p200 family protein p204, which is known to be involved in the differentiation of skeletal muscle myotubes, cardiac myocytes, and macrophages, also serves as a cofactor of Cbfa1 and promotes osteogenesis. In this study we established that suppression of p204 expression by an adenovirus construct encoding p204 antisense RNA inhibited osteoblast-specific gene activation by Cbfa1 in an osteogenesis assay involving the pluripotent C2C12 mesenchymal cell line. Using protein-protein interaction assays we established that Cbfa1, pRb, and p204 form a ternary complex in which pRb serves as a linker connecting p204 and Cbfa1. Chromatin immunoprecipitation assays revealed the binding of such a p204-pRbCbfa1 transcription factor complex to the promoter of the osteocalcin gene. The pRb requirement of the stimulation of Cbfa1 activity by p204 was established in experiments involving p204 mutants lacking one or two pRb binding (LXCXE) motifs. Such mutants failed to enhance the Cbfa1-dependent transactivation of gene expression as well as osteogenesis. Furthermore, as revealed in reporter gene and in vitro osteogenesis assays p204 synergized with pRb in the stimulation of Cbfa1-dependent gene activation and osteoblast differentiation.

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p205, A potential tumor suppressor, inhibits cell proliferation via multiple pathways of cell cycle regulation

Cited by 30 publications

References 38 publications

Proteomics-based investigation in C2C12 myoblast differentiation

Proteomics-based investigation in C2C12 myoblast differentiation

p204 Protein Overcomes the Inhibition of Core Binding Factor α-1–mediated Osteogenic Differentiation by Id Helix-Loop-Helix Proteins

The Retinoblastoma Protein Is an Essential Mediator of Osteogenesis That Links the p204 Protein to the Cbfa1 Transcription Factor Thereby Increasing Its Activity

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