Cytokine response gene 8 (CR8) regulates the cell cycle G1-S phase transition and promotes cellular survival

Beadling, Carol; Cereseto, Anna; Fan, Wen; Naramura, Mayumi; Smith, Kendall A.

doi:10.1038/sj.onc.1204212

Cited by 7 publications

(8 citation statements)

References 33 publications

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“…However, the molecular mechanisms through which Stra13 regulates these diverse biological responses are largely unclear. Previous studies have shown that Stra13 overexpression results in growth suppression, cell cycle arrest, and cellular senescence, which are important tumor suppression mechanisms [4], [6], [10], [12], [17]. Consistent with these observations, Stra13 expression is indeed down regulated in some tumors.…”

Section: Introductionsupporting

confidence: 78%

SUMO Modification of Stra13 Is Required for Repression of Cyclin D1 Expression and Cellular Growth Arrest

et al. 2012

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Stra13, a basic helix-loop-helix (bHLH) transcription factor is involved in myriad biological functions including cellular growth arrest, differentiation and senescence. However, the mechanisms by which its transcriptional activity and function are regulated remain unclear. In this study, we provide evidence that post-translational modification of Stra13 by Small Ubiquitin-like Modifier (SUMO) dramatically potentiates its ability to transcriptionally repress cyclin D1 and mediate G1 cell cycle arrest in fibroblast cells. Mutation of SUMO acceptor lysines 159 and 279 located in the C-terminal repression domain has no impact on nuclear localization; however, it abrogates association with the co-repressor histone deacetylase 1 (HDAC1), attenuates repression of cyclin D1, and prevents Stra13-mediated growth suppression. HDAC1, which promotes cellular proliferation and cell cycle progression, antagonizes Stra13 sumoylation-dependent growth arrest. Our results uncover an unidentified regulatory axis between Stra13 and HDAC1 in progression through the G1/S phase of the cell cycle, and provide new mechanistic insights into regulation of Stra13-mediated transcriptional repression by sumoylation.

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Section: Introductionsupporting

confidence: 78%

SUMO Modification of Stra13 Is Required for Repression of Cyclin D1 Expression and Cellular Growth Arrest

et al. 2012

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“…In contrast, loss of Stra13 results in reduced apoptosis of lymphocytes Thin et al 2007), and its overexpression results in increased cell death in 293T cells (Ivanova et al 2004). The down regulation of Stra13 in lung and colon cancer is consistent with many previous studies demonstrating that Stra13 causes growth arrest in a number of cell types (Sun and Taneja, 2000;Beadling et al 2001;Li et al 2002;Zawel et al 2002;Seimiya et al 2004), as well as the fact that it is expressed in most normal tissues that are differentiated Ivanova et al 2005;Sun et al 2007). Moreover, Stra13 promotes differentiation of a number of cell types such as chondrocytes (Shen et al 2002), osteoblasts (Iwata et al 2006), trophoblasts (Hughes et al 2004), and neurons (Boudjelal et al 1997).…”

Section: Discussionsupporting

confidence: 77%

“…The fi rst member was called Stimulated with retinoic acid 13 (Stra13) (Boudjelal et al 1997) or Clast5 (Seimiya et al 2002) in mouse, Differentially Expressed in Chondrocytes (Dec1) (Shen et al 1997), E47 interacting protein 1 (Eip1) (Dear et al 1997) or Cytokine response gene 8 (CR-8) (Beadling et al 2001) in human, and Enhancer-ofSplit and Hairy-related protein-2 (Sharp-2) in rat (Rossner et al 1997). Similarly, the other member was called Sharp-1 in rat (Rossner et al 1997) and mouse (Azmi and Taneja, 2002) and Dec2 in human (Fujimoto et al 2001).…”

Section: The Hey Subfamilymentioning

confidence: 99%

bHLH-Orange Transcription Factors in Development and Cancer

Sun

Ghaffari²,

Taneja

2007

Translational Oncogenomics

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Basic helix-loop-helix (bHLH) proteins are a large superfamily of transcription factors that play critical roles in many physiological processes including cellular differentiation, cell cycle arrest and apoptosis. Based on structural and phylogenetic analysis, mammalian bHLH-Orange (bHLH-O) proteins, which constitute the repressor family of bHLH factors, can be grouped into four subfamilies: Hes, Hey, Helt and Stra13/Dec. In addition to the bHLH domain that mediates DNA-binding and protein dimerization, all members of this family are characterized by a distinctive motif called the "Orange domain" which is present exclusively in these factors. Genetic studies using targeted mutagenesis in mice have revealed essential roles for many bHLH-O genes in embryonic development, cell fate decisions, differentiation of a number of cell types and in apoptosis. Furthermore, growing evidence of crosstalk between bHLH-O proteins with the tumor suppressors p53 and hypoxia-inducible factor, have started to shed light on their possible roles in oncogenesis. Consistently, deregulated expression of several bHLH-O factors is associated with various human cancers. Here, we review the structure and biological functions of bHLH-O factors, and discuss recent studies that suggest a potential role for these factors in tumorigenesis and tumor progression.

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“…Stra13 expression is inducible by several stimuli in different cell types, and gain of function in cultured cells has demonstrated its role in the regulation of cellular differentiation, cell cycle arrest, stress response, and apoptosis. For instance, the overexpression of Stra13 in many cell types causes cell cycle arrest (Sun and Taneja, 2000; Beadling et al, 2001; Li et al, 2002; Seimiya et al, 2002) and promotes neurogenic and chondrogenic differentiation (Boudjelal et al, 1997; Shen et al, 2002) but inhibits adipogenesis (Yun et al, 2002). We have previously shown that Stra13-null mice exhibit defects in T cell activation, which leads to the development of a lupus-like autoimmune disorder (H. Sun et al, 2001) as well as defects in radiation-induced apoptosis (Thin et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Stra13 regulates satellite cell activation by antagonizing Notch signaling

Sun

Vercherat

et al. 2007

The Journal of Cell Biology

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Satellite cells play a critical role in skeletal muscle regeneration in response to injury. Notch signaling is vital for satellite cell activation and myogenic precursor cell expansion but inhibits myogenic differentiation. Thus, precise spatial and temporal regulation of Notch activity is necessary for efficient muscle regeneration. We report that the basic helix-loop-helix transcription factor Stra13 modulates Notch signaling in regenerating muscle. Upon injury, Stra13−/− mice exhibit increased cellular proliferation, elevated Notch signaling, a striking regeneration defect characterized by degenerated myotubes, increased mononuclear cells, and fibrosis. Stra13−/− primary myoblasts also exhibit enhanced Notch activity, increased proliferation, and defective differentiation. Inhibition of Notch signaling ex vivo and in vivo ameliorates the phenotype of Stra13−/− mutants. We demonstrate in vitro that Stra13 antagonizes Notch activity and reverses the Notch-imposed inhibition of myogenesis. Thus, Stra13 plays an important role in postnatal myogenesis by attenuating Notch signaling to reduce myoblast proliferation and promote myogenic differentiation.

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Cytokine response gene 8 (CR8) regulates the cell cycle G1-S phase transition and promotes cellular survival

Cited by 7 publications

References 33 publications

SUMO Modification of Stra13 Is Required for Repression of Cyclin D1 Expression and Cellular Growth Arrest

SUMO Modification of Stra13 Is Required for Repression of Cyclin D1 Expression and Cellular Growth Arrest

bHLH-Orange Transcription Factors in Development and Cancer

Stra13 regulates satellite cell activation by antagonizing Notch signaling

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