Retinoblastoma Protein Is Functionally Distinct from Its Homologues in Affecting Glucocorticoid Receptor-mediated Transcription and Apoptosis

Singh, Paramjeet; Chan, Siew Wee; Hong, Wanjin

doi:10.1074/jbc.m100137200

Cited by 16 publications

(13 citation statements)

References 47 publications

(67 reference statements)

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“…20 GC-mediated transcription and apoptosis are dependent on Rb and on the transcription of the coactivator hBRM but not of its homologues p170 and p130. 21 These findings support the idea that although the three members may complement each other, they are not fully functional or redundant. 22 However, the in vivo mechanisms of cell growth arrest by GC and the relative modes of resistance in childhood ALL remain still unclear.…”

Section: Introductionsupporting

confidence: 79%

Glucocordicoids induce G1 Arrest of Lymphoblastic Cells through Retinoblastoma Protein Rb1 Dephosphorylation in Childhood Acute Lymphoblastic Leukemia In Vivo

Addeo¹,

Casale²,

Caraglia³

et al. 2004

Cancer Biology & Therapy

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Section: Introductionsupporting

confidence: 79%

Glucocordicoids induce G1 Arrest of Lymphoblastic Cells through Retinoblastoma Protein Rb1 Dephosphorylation in Childhood Acute Lymphoblastic Leukemia In Vivo

Addeo¹,

Casale²,

Caraglia³

et al. 2004

Cancer Biology & Therapy

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“…The molecular mechanism by which Rb affects glucocorticoid responses is thought to involve E2F as well as a direct interaction between glucocorticoid receptors (GR) and Rb. Glucocorticoid-induced apoptosis has been shown to be dependent upon the Rb binding of the transcriptional coactivator hBRM and subsequent potentiation of GR-induced transcription of target genes (Singh et al 2001). In parallel, dexamethasone-induced hypophosphorylation of Rb results in decreased activation of E2F-responsive genes and subsequent cell-cycle arrest (Greenberg et al 2002).…”

Section: Molecular Mechanism Of Action Of Mifmentioning

confidence: 99%

Macrophage migration inhibitory factor: a neuroendocrine modulator of chronic inflammation

Baugh¹,

Donnelly²

2003

Journal of Endocrinology

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The diverse actions of macrophage migration inhibitory factor (MIF) within the immuno-neuroendocrine system are yet to be fully understood, but it is clear that MIF plays a pivotal role in the regulation of both the innate and adaptive immune response. An emerging body of data presently indicates that MIF's position within the cytokine cascade is to act in concert with glucocorticoids to control the 'set point' and magnitude of the immune and inflammatory response.In this article we will review the actions of MIF within the immune system and discuss the overlapping and contrasting aspects of MIF and glucocorticoid biology. In particular we will focus on the role of MIF within the immuno-neuroendocrine interface and suggest molecular mechanisms by which MIF may counter-regulate glucocorticoid function. Finally we will discuss emerging evidence that functional MIF gene-promoter polymorphisms render one susceptible to elevated MIF expression, and the development of an exaggerated immune/ inflammatory response that potentiates the progression to chronic inflammatory disease.

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“…A role for Rb in skeletal muscle differentiation in the mouse has also been demonstrated (47). The available evidence suggests that pRb regulates differentiation by influencing the activity of a number of differentiation-promoting transcription factors such as MyoD (11,27,28), the glucocorticoid receptor (35,36), C/EBP␤ (2-4), and CBFA1 (40). The potential clinical importance of these observations is suggested by the identification of naturally occurring Rb mutants whose protein products fail to interact with E2F, yet which maintain the ability to promote differentiation (19,34).…”

mentioning

confidence: 99%

Genetic Interaction between Rb and K-ras in the Control of Differentiation and Tumor Suppression

Takahashi

Contreras

Bronson

et al. 2004

Molecular and Cellular Biology

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Although the retinoblastoma protein (pRb) has been implicated in the processes of cellular differentiation, there is no compelling genetic or in vivo evidence that such activities contribute to pRb-mediated tumor suppression. Motivated by cell culture studies suggesting that Ras is a downstream effector of pRb in the control of differentiation, we have examined the tumor and developmental phenotypes of Rb and K-ras double-knockout mice. We find that heterozygosity for K-ras (i) rescued a unique subset of developmental defects that characterize Rb-deficient embryos by affecting differentiation but not proliferation and (ii) significantly enhanced the degree of differentiation of pituitary adenocarcinomas arising in Rb heterozygotes, leading to their prolonged survival. These observations suggest that Rb and K-ras function together in vivo, in the contexts of both embryonic and tumor development, and that the ability to affect differentiation is a major facet of the tumor suppressor function of pRb.Inheritance of a mutated allele of the retinoblastoma gene (Rb) predisposes to familial retinoblastoma, and Rb is also frequently inactivated in sporadic human cancers of diverse histological origins (10). Mice heterozygous for Rb develop pituitary adenocarcinomas and thyroid adenomas (13)(14)(15)44), suggesting that the mouse can be used to understand the pathways through which Rb exerts its tumor suppressor functions. Further, nullizygosity for Rb results in lethality at midgestation, with embryos displaying defects in proliferation and differentiation (5,15,21,47). Thus, the combined analysis of Rb ϩ/Ϫ and Rb Ϫ/Ϫ mice provides an opportunity to dissect the functions of the retinoblastoma protein (pRb) that contribute to its tumor suppressor functions.pRb is best characterized for its role in controlling proliferation; this is accomplished through its regulated interaction with the E2F family of transcription factors (9). The significance of pRb-mediated inhibition of proliferation through E2F has been analyzed in the mouse. Rb Ϫ/Ϫ embryos display cellautonomous deregulated proliferation in tissues such as the central nervous system (CNS) and lens (7,25,45), and compound embryos lacking Rb and E2f1, E2f2, or E2f3 show reduced levels of ectopic DNA replication in these tissues (33,41,49). Mirroring the effects seen during embryonic development, loss of E2f1 or E2f3 significantly reduced the frequency of grossly detectable pituitary tumors (46, 48), suggesting that deregulated proliferation, mediated by E2f, contributes to tumor formation following loss of Rb.Cell culture-based experiments suggest that pRb also participates in several differentiation programs such as adipogenesis (3, 6), osteogenesis (34, 40), and myogenesis (11,27). A role for Rb in skeletal muscle differentiation in the mouse has also been demonstrated (47). The available evidence suggests that pRb regulates differentiation by influencing the activity of a number of differentiation-promoting transcription factors such as MyoD (11,27,28), the glucocort...

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Retinoblastoma Protein Is Functionally Distinct from Its Homologues in Affecting Glucocorticoid Receptor-mediated Transcription and Apoptosis

Cited by 16 publications

References 47 publications

Glucocordicoids induce G1 Arrest of Lymphoblastic Cells through Retinoblastoma Protein Rb1 Dephosphorylation in Childhood Acute Lymphoblastic Leukemia In Vivo

Glucocordicoids induce G1 Arrest of Lymphoblastic Cells through Retinoblastoma Protein Rb1 Dephosphorylation in Childhood Acute Lymphoblastic Leukemia In Vivo

Macrophage migration inhibitory factor: a neuroendocrine modulator of chronic inflammation

Genetic Interaction between Rb and K-ras in the Control of Differentiation and Tumor Suppression

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