Retinoblastoma protein complexes with C/EBP proteins and activates C/EBP‐mediated transcription*

Charles, A.; Tang, Xiaoou; Crouch, Erika C.; Brody, Jerome S.; Xiao, Zhi‐Xiong Jim

doi:10.1002/jcb.1239

Cited by 44 publications

(36 citation statements)

References 50 publications

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“…differentiation program. In fact, several epidermal-specific proteins are regulated by transcriptional elements such as Sp1 or C/EBP Kaufman et al, 2002;Kumar and Butler, 1999;Maytin and Habener, 1998;Maytin et al, 1999;Oh and Smart, 1998;Park and Morasso, 1999;Sinha and Fuchs, 2001;Zhu et al, 2002), which are themselves modulated by retinoblastoma family proteins (Charles et al, 2001;Chen et al, 1996;Classon et al, 2000;Decesse et al, 2001;Rohde et al, 1996;Udvadia et al, 1995). Conversely, we previously observed decreased E2f4 expression in terminally differentiating human keratinocytes, and most of the protein is bound by p107 and p130 (Paramio et al, 2000).…”

Section: Discussionmentioning

confidence: 73%

Abnormal epidermal differentiation and impaired epithelial-mesenchymal tissue interactions in mice lacking the retinoblastoma relatives p107 and p130

et al. 2003

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The functions of p107 and p130, members of the retinoblastoma family, include the control of cell cycle progression and differentiation in several tissues. Our previous studies suggested a role for p107 and p130 in keratinocyte differentiation in vitro. We now extend these data using knockout animal models. We found impaired terminal differentiation in the interfollicular keratinocytes of p107/p130-double-null mice epidermis. In addition, we observed a decreased number of hair follicles and a clear developmental delay in hair, whiskers and tooth germs. Skin grafts of p107/p130-deficient epidermis onto NOD/scid mice showed altered differentiation and hyperproliferation of the interfollicular keratinocytes, thus demonstrating that the absence of p107 and p130 results in the deficient control of differentiation in keratinocytes in a cell-autonomous manner. Besides normal hair formation, follicular cysts, misoriented and dysplastic follicles, together with aberrant hair cycling, were also observed in the p107/p130 skin transplants. Finally, the hair abnormalities in p107/p130-null skin were associated with altered Bmp4-dependent signaling including decreased ∆Np63 expression. These results indicate an essential role for p107 and p130 in the epithelial-mesenchimal interactions.

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Section: Discussionmentioning

confidence: 73%

Abnormal epidermal differentiation and impaired epithelial-mesenchymal tissue interactions in mice lacking the retinoblastoma relatives p107 and p130

et al. 2003

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“…It is well established that Rb family members regulate the expression of differentiation markers through direct interaction with transcription factors, such as MyoD in muscle (Novitch, 1996) and C/EBPβ in lung fibroblasts (Chen, 1996). Interestingly, C/EBPβ controls proliferation in keratinocytes and directly regulates the expression of K10 (Zhu, 1999;Maytin, 1999;Charles, 2001). However, we did not find any alterations in C/EBPβ activity during differentiation of Rbdeficient keratinocytes compared with control cells (not shown), suggesting that this transcription factor is not deregulated in Rb-deficient keratinocytes.…”

Section: Discussionmentioning

confidence: 99%

Unique and overlapping functions of pRb and p107 in the control of proliferation and differentiation in epidermis

Ruíz¹,

Santos²,

Segrelles³

et al. 2004

Development

133

197

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The retinoblastoma gene product, pRb, plays a crucial role in cell cycle regulation, differentiation and inhibition of oncogenic transformation. pRb and its closely related family members p107 and p130 perform exclusive and overlapping functions during mouse development. The embryonic lethality of Rb-null animals restricts the phenotypic analysis of these mice to mid-gestation embryogenesis. We employed the Cre/loxP system to study the function of Rb in adult mouse stratified epithelium. RbF19/F19;K14cre mice displayed hyperplasia and hyperkeratosis in the epidermis with increased proliferation and aberrant expression of differentiation markers. In vitro, pRb is essential for the maintainance of the postmitotic state of terminally differentiated keratinocytes, preventing cell cycle re-entry. However, p107 compensates for the effects of Rb loss as the phenotypic abnormalities of RbF19/F19;K14cre keratinocytes in vivo and in vitro become more severe with the concurrent loss of p107 alleles. p107 alone appears to be dispensable for all these phenotypic changes, as the presence of a single Rb allele in a p107-null background rescues all these alterations. Luciferase reporter experiments indicate that these phenotypic alterations might be mediated by increased E2F activity. Our findings support a model in which pRb in conjunction with p107 plays a central role in regulating epidermal homeostasis.

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“…Rb not only binds transcription factors involved in cell cycle progression, it also interacts with transcription factors involved in differentiation (7,14,15). Rb has been shown to bind to members of the CCAAT/enhancer binding protein (C/EBP) family of transcription factors (2)(3)(4).…”

mentioning

confidence: 99%

Rb regulates C/EBPβ-DNA-binding activity during 3T3-L1 adipogenesis

Cole¹,

Harmon²,

Harp³

et al. 2004

American Journal of Physiology-Cell Physiology

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Two pathways are initiated upon 3T3-L1 preadipocyte differentiation: the reentry of cells into the cell cycle and the initiation of a cascade of transcriptional events that “prime” the cell for differentiation. The “priming” event involves the synthesis of members of the CCAAT/enhancer binding protein (C/EBP) family of transcription factors. However, the relationship between these two pathways is unknown. Here we report that in the 3T3-L1 preadipocytes induced to differentiate, cell cycle progression and the initiation of differentiation are linked by a cell cycle-dependent Rb-C/EBPβ interaction. Cell cycle arrest in G1 by l-mimosine inhibited differentiation-induced C/EBPβ-DNA-binding activity and Rb phosphorylation. However, cell cycle arrest after the G1/S transition by aphidicolin or nocodazole did not prevent C/EBPβ-DNA-binding activity or Rb phosphorylation. Furthermore, hypophosphorylated Rb and C/EBPβ coimmunoprecipitated, whereas phosphorylated Rb and C/EBPβ did not. Electrophoretic mobility shift assays demonstrated that recombinant hypophosphorylated Rb decreased C/EBPβ-DNA-binding activity and that Rb overexpression inhibited C/EBPβ-induced transcriptional activation of a C/EBPα-promoter-luciferase reporter gene. We conclude that C/EBPβ-DNA-binding activity is regulated by its interaction with hypophosphorylated Rb, thereby linking the progression of the cell cycle to the initiation of differentiation during 3T3-L1 adipogenesis.

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Retinoblastoma protein complexes with C/EBP proteins and activates C/EBP‐mediated transcription*

Cited by 44 publications

References 50 publications

Abnormal epidermal differentiation and impaired epithelial-mesenchymal tissue interactions in mice lacking the retinoblastoma relatives p107 and p130

Abnormal epidermal differentiation and impaired epithelial-mesenchymal tissue interactions in mice lacking the retinoblastoma relatives p107 and p130

Unique and overlapping functions of pRb and p107 in the control of proliferation and differentiation in epidermis

Rb regulates C/EBPβ-DNA-binding activity during 3T3-L1 adipogenesis

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