Id2 and Id3 Define the Potency of Cell Proliferation and Differentiation Responses to Transforming Growth Factor β and Bone Morphogenetic Protein

Kowanetz, Marcin; Valcourt, Ulrich; Bergström, Rosita; Heldin, Carl‐Henrik; Moustakas, Aristidis

doi:10.1128/mcb.24.10.4241-4254.2004

Cited by 309 publications

(347 citation statements)

References 46 publications

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“…The transcriptional response to stimulation with BMP has been analyzed in different cellular systems [5,[29][30][31] , but not previously in cells of lymphoid origin. Up-regulation of ID genes is an important event in this response, and has been demonstrated to be dependent on Smad phosphorylation [8].…”

Section: Discussionmentioning

confidence: 99%

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Inhibitory effects and target genes of bone morphogenetic protein 6 in Jurkat TAg cells

et al. 2007

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Bone morphogenetic proteins (BMP) are multifunctional cytokines that belong to the TGF-b superfamily. BMP have been shown to regulate haematopoietic stem cells, B lymphopoiesis and early thymocyte differentiation. In the present study we explored the role of BMP-6 in Jurkat TAg cells. BMP-6 rapidly induced phosphorylation of Smad1/5/8, p38 and ERK1/2, followed by a potent up-regulation of ID1, ID2 and ID3. ID1 and ID3 were also induced at the protein level. Genome-wide expression profiling of cells treated with BMP-6 compared to medium confirmed that ID1-ID3 were target genes of BMP-6 together with Noggin and Smad6. Furthermore, several genes involved in transcriptional regulation were also identified, including NFKBIA, HEY1, DLX2, KLF10 and early growth response 1. Stimulation with BMP-6 exerted an antiproliferative effect that was counteracted by inhibitor of DNA binding (Id)1 siRNA, indicating that Id1 is an important downstream mediator in Jurkat TAg cells. A subset of CD4 + T cells were found to express the BMP receptors Alk-2 and Alk-3 (type I), in addition to BMPRII (type II). BMP-6 also induced phosphorylation of Smad1/5/8, followed by transcriptional increase in ID1-ID3 mRNA expression. However, we did not observe significant changes in Id protein expression in CD4 + T cells. Altogether, the data indicate a role for BMP-6 in human T lineage cells.

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Section: Discussionmentioning

confidence: 99%

“…Several studies have pointed toward members of the inhibitor of DNA binding (Id) protein family, a class of helix-loop-helix (HLH) proteins, as important targets for BMP signalling [5][6][7][8]. HLH proteins act as transcriptional regulators and are essential factors for lymphoid development and function [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effects and target genes of bone morphogenetic protein 6 in Jurkat TAg cells

et al. 2007

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“…Controls were performed using a b-galactosidase-encoding virus and the cells were stained with 5-bromo-4-chloro-3-indolyl-b-D-galactoside (X-Gal, Eurogentec, France) as described by Fujii et al 39 Relatively high MOI had to be used in order to overexpress the Smad-6 as well as the control b-Gal proteins, but the use of similar MOI with similar viruses was published in mammary carcinoma cells. 40 Nevertheless, transgenes were transcribed efficiently ( Figures 4A and 5B), and despite the slight cell toxicity of the AdV, no perturbation in the commitment to the neural cell lineage was observed ( Figure 4C). Under optimal conditions, more than 90% of the cells were infected.…”

Section: Sox-1-gfp Determinationmentioning

confidence: 96%

BMP-4 induces a Smad-dependent apoptotic cell death of mouse embryonic stem cell-derived neural precursors

et al. 2005

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Embryonic ectoderm is fated to become either neural or epidermal, depending on patterning processes that occur before and during gastrulation. It has been stated that epidermal commitment proceeds from a bone morphogenetic protein-4 (BMP-4)-dependent inhibition of dorsal ectoderm neuralization. We recently demonstrated that murine embryonic stem (ES) cells treated with BMP-4 undergo effective keratinocyte commitment and epidermogenesis. Focusing on the precise role of BMP-4 in the early choice between neural and epidermal commitment, we show here that BMP-4 treatment of ES cells leads to a dramatic apoptotic death of Sox-1 þ neural precursors with concomitant epidermal engagement. In addition, neutralization of the Smad pathway prevents both the BMP-4 apoptotic process and the inhibition of neural differentiation. Our results suggest that, in mammals, BMP-4, as an active inducer of epidermal commitment, interferes with the survival of neural precursors through induction of their apoptotic cell death.

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“…Thus, in addition to TGF-b (Ling et al, 2002;Kretschmer et al, 2003;Siegel et al, 2003;Kowanetz et al, 2004), activin was identified as a novel regulator of Id gene expression. Similar to TGF-b, activin has opposite effects on keratinocytes and fibroblasts.…”

Section: Id Proteins In Epidermal Homeostasismentioning

confidence: 99%

“…Id genes are known targets of TGF-b and BMP signaling, and they are regulated in a cell-type-specific manner by these factors (Korchynskyi and ten Dijke, 2002;Kurisaki et al, 2003;Kowanetz et al, 2004). However, their physiological roles in the TGF-b/BMP signaling pathways are still poorly understood.…”

mentioning

confidence: 99%

Id proteins: Novel targets of activin action, which regulate epidermal homeostasis

et al. 2005

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Activin is a member of the transforming growth factor b (TGF-b) family, which plays a crucial role in skin morphogenesis and wound healing. To gain insight into the underlying mechanisms of action, we searched for activin-regulated genes in cultured keratinocytes. One of the identified target genes encodes Id1, a negative regulator of helix-loop-helix transcription factors. We show that Id1, Id2, and Id3 are strongly downregulated by activin in keratinocytes in vitro and in vivo. To determine the role of Id1 in keratinocyte biology, we generated stable HaCaT keratinocyte cell lines overexpressing this protein. Our results revealed that enhanced levels of Id1 do not affect proliferation of keratinocytes in monoculture under exponential culture conditions or in response to activin or TGF-b1. However, in three-dimensional organotypic cultures, Id1-overexpressing HaCaT cells formed a hyperthickened and disorganized epithelium that was characterized by enhanced keratinocyte proliferation, abnormal differentiation, and an increased rate of apoptosis. These results identify an important function of Id1 in the regulation of epidermal homeostasis.

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Id2 and Id3 Define the Potency of Cell Proliferation and Differentiation Responses to Transforming Growth Factor β and Bone Morphogenetic Protein

Cited by 309 publications

References 46 publications

Inhibitory effects and target genes of bone morphogenetic protein 6 in Jurkat TAg cells

Inhibitory effects and target genes of bone morphogenetic protein 6 in Jurkat TAg cells

BMP-4 induces a Smad-dependent apoptotic cell death of mouse embryonic stem cell-derived neural precursors

Id proteins: Novel targets of activin action, which regulate epidermal homeostasis

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