REST In Good Times and Bad:  Roles In Tumor Suppressor and Oncogenic Activities

Majumder, Sadhan

doi:10.4161/cc.5.17.2982

Cited by 109 publications

(105 citation statements)

References 52 publications

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“…11 This remarkable flexibility in all aspects of REST regulation is consistent with our emerging appreciation for the decidedly context-specific effects of REST for establishing and maintaining cell identity and function. Indeed, REST and CoREST seem to play important roles in a growing number of normal and pathological cell types, including embryonic stem cells (ESCs) [12][13][14][15][16][17][18] and cancer [19][20][21][22][23][24][25][26][27][28] cells. In this review, we focus on understanding the evolving roles of REST and CoREST in transcriptional and epigenetic regulation of seminal neural cell fate decisions.…”

Section: Introductionmentioning

confidence: 99%

REST and CoREST are transcriptional and epigenetic regulators of seminal neural fate decisions

Qureshi

Gökhan²,

Mehler³

2010

Cell Cycle

126

107

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Section: Introductionmentioning

confidence: 99%

REST and CoREST are transcriptional and epigenetic regulators of seminal neural fate decisions

Qureshi

Gökhan²,

Mehler³

2010

Cell Cycle

126

107

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“…REST is believed to be a major transcriptional repressor of neurogenesis [2][3][4][5] , and activation of REST target genes was found to be sufficient to convert neural stem/progenitor cells to neuronal phenotypes 6,7 . However, REST activity seems to depend on the cellular context; for example, REST can show both an oncogenic [8][9][10] and tumour-suppressor function 5 as well as involvement in haematopoietic and cardiac differentiation [3][4][5] .…”

mentioning

confidence: 99%

“…However, REST activity seems to depend on the cellular context; for example, REST can show both an oncogenic [8][9][10] and tumour-suppressor function 5 as well as involvement in haematopoietic and cardiac differentiation [3][4][5] . Embryonic stem (ES) cells are pluripotent cells that have the potential for both indefinite selfrenewal and differentiation into all three germ layers of the body 11 .…”

mentioning

confidence: 99%

REST maintains self-renewal and pluripotency of embryonic stem cells

Singh

Kagalwala

Parker-Thornburg³

et al. 2008

Nature

309

285

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The neuronal repressor REST (RE1-silencing transcription factor; also called NRSF) is expressed at high levels in mouse embryonic stem (ES) cells 1 , but its role in these cells is unclear. Here we show that REST maintains self-renewal and pluripotency in mouse ES cells through suppression of the microRNA miR-21. We found that, as with known self-renewal markers, the level of REST expression is much higher in self-renewing mouse ES cells than in differentiating mouse ES (embryoid body, EB) cells. Heterozygous deletion of Rest (Rest 1/2 ) and its short-interfering-RNA-mediated knockdown in mouse ES cells cause a loss of self-renewal-even when these cells are grown under self-renewal conditions-and lead to the expression of markers specific for multiple lineages. Conversely, exogenously added REST maintains self-renewal in mouse EB cells. Furthermore, Rest 1/2 mouse ES cells cultured under self-renewal conditions express substantially reduced levels of several self-renewal regulators, including Oct4 (also called Pou5f1), Nanog, Sox2 and c-Myc, and exogenously added REST in mouse EB cells maintains the self-renewal phenotypes and expression of these self-renewal regulators. We also show that in mouse ES cells, REST is bound to the gene chromatin of a set of miRNAs that potentially target self-renewal genes. Whereas mouse ES cells and mouse EB cells containing exogenously added REST express lower levels of these miRNAs, EB cells, Rest 1/2 ES cells and ES cells treated with short interfering RNA targeting Rest express higher levels of these miRNAs. At least one of these REST-regulated miRNAs, miR-21, specifically suppresses the self-renewal of mouse ES cells, corresponding to the decreased expression of Oct4, Nanog, Sox2 and c-Myc. Thus, REST is a newly discovered element of the interconnected regulatory network that maintains the self-renewal and pluripotency of mouse ES cells.REST is believed to be a major transcriptional repressor of neurogenesis 2-5 , and activation of REST target genes was found to be sufficient to convert neural stem/progenitor cells to neuronal phenotypes 6,7 . However, REST activity seems to depend on the cellular context; for example, REST can show both an oncogenic 8-10 and tumour-suppressor function 5 as well as involvement in haematopoietic and cardiac differentiation [3][4][5] . Embryonic stem (ES) cells are pluripotent cells that have the potential for both indefinite selfrenewal and differentiation into all three germ layers of the body 11 . Here we provide evidence that REST has a unique role as a protector of self-renewal and pluripotency in mouse ES cells, corresponding to the expression of critical regulators such as Oct4, Nanog, Sox2 and c-Myc.We began by assessing the levels of REST protein in mouse ES cells growing under self-renewal conditions and differentiation conditions ( Fig. 1a; ES and EB, respectively). As expected, western blotting showed that the ES cells had higher levels of REST expression and of the representative markers of self-renewal (proteins Oct4, Sox2 and c-M...

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“…The profound context-specificity of the functional repertoire of REST is further highlighted by its dual role as a tumor suppressor and oncoprotein [36][37][38] .…”

Section: Discussionmentioning

confidence: 99%

Involvement of REST corepressor 3 in prognosis of human hepatitis B

Xue

Zheng

et al. 2011

Acta Pharmacol Sin

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Aim: To examine the potential correlation between serum REST corepressor 3 (RCOR3) level and the outcome of patients with hepatitis B. Methods: Concanavalin A (ConA)-induced mouse hepatitis model was used. The mRNA level of RCOR3 in mouse liver was measured using GeneChip array and real-time PCR. One hundred seventy-seven patients with hepatitis B and 34 healthy individuals were categorized into six groups including mild chronic hepatitis, moderate chronic hepatitis B, severe hepatitis B (SHB), cirrhosis, hepatocellular carcinoma (HCC) and healthy control. Serum levels of human RCOR3 were measured using ELISA. Results: In the mouse hepatitis model, the mRNA level of RCOR3 in liver was reduced early after exposure to ConA, then increased after 6 h of exposure. There was no significant difference in the serum RCOR3 level between the mild chronic hepatitis B and the control groups. The serum RCOR3 level was significantly increased in the moderate chronic hepatitis B group, but significantly reduced in SHB, cirrhosis and HCC groups, as compared with the control group. Moreover, the serum RCOR3 levels in SHB, cirrhosis and liver cancer patients were significantly lower than those in the patients with moderate chronic hepatitis B and with mild chronic hepatitis B. Rank correlation analysis revealed a significant correlation between serum RCOR3 level and total bilirubin (r=-0.305, P<0.01). There was no significant correlation between RCOR3 on one hand, and alanine transaminase (r=0.014, P>0.05) or aspartate transaminase (r=-0.079, P>0.05) on the other hand. Conclusion: Serum RCOR3 level may reflect the degree of liver damage, which might be a potential biomarker for the outcome of patients with hepatitis B.

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REST In Good Times and Bad: Roles In Tumor Suppressor and Oncogenic Activities

Cited by 109 publications

References 52 publications

REST and CoREST are transcriptional and epigenetic regulators of seminal neural fate decisions

REST and CoREST are transcriptional and epigenetic regulators of seminal neural fate decisions

REST maintains self-renewal and pluripotency of embryonic stem cells

Involvement of REST corepressor 3 in prognosis of human hepatitis B

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