The Human Candidate Tumor Suppressor Gene <i>HIC1</i> Recruits CtBP through a Degenerate GLDLSKK Motif

Deltour, Sophie; Pinte, Sébastien; Guérardel, Cateline; Wasylyk, Bohdan; Leprince, Dominique

doi:10.1128/mcb.22.13.4890-4901.2002

Cited by 89 publications

(167 citation statements)

References 58 publications

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“…Anti-CtBP antibodies were from Santa Cruz Biotechnology (Santa Cruz, CA) and Upstate Biotechnologies (Lake Placid, NY). Anti-HIC1 antibody was described by Deltour et al (23).…”

Section: Methodsmentioning

confidence: 99%

“…We conclude from these studies that 2-DG effectively changes the redox status of primary CCD fibroblasts. SIRT1 transcription is repressed by HIC1 (20), whose function depends in part on its interaction with the corepressor, CtBP (23). We reasoned, therefore, that conditions that decreased the association of HIC1 with CtBP would decrease the HIC1-mediated repression, hence increasing SIRT1 expression.…”

Section: -Dgmentioning

confidence: 99%

“…3A Right). To confirm that this lack of response was due to the absence of HIC1, we transfected H1299 cells with a HIC1 expression vector (23). Addition of HIC1 reduced SIRT1 transcript levels and restored the response to 2-DG (Fig.…”

Section: -Dgmentioning

confidence: 99%

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RETRACTED: Metabolic regulation of SIRT1 transcription via a HIC1:CtBP corepressor complex

Zhang

Wang

Fleuriel

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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The Sir2 histone deacetylases are important for gene regulation, metabolism, and longevity. A unique feature of these enzymes is their utilization of NAD + as a cosubstrate, which has led to the suggestion that Sir2 activity reflects the cellular energy state. We show that SIRT1, a mammalian Sir2 homologue, is also controlled at the transcriptional level through a mechanism that is specific for this isoform. Treatment with the glycolytic blocker 2-deoxyglucose (2-DG) decreases association of the redox sensor CtBP with HIC1, an inhibitor of SIRT1 transcription. We propose that the reduction in transcriptional repression mediated by HIC1, due to the decrease of CtBP binding, increases SIRT1 expression. This mechanism allows the specific regulation of SIRT1 in response to nutrient deprivation.

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“…Anti-CtBP antibodies were from Santa Cruz Biotechnology (Santa Cruz, CA) and Upstate Biotechnologies (Lake Placid, NY). Anti-HIC1 antibody was described by Deltour et al (23).…”

Section: Methodsmentioning

confidence: 99%

Section: -Dgmentioning

confidence: 99%

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RETRACTED: Metabolic regulation of SIRT1 transcription via a HIC1:CtBP corepressor complex

Zhang

Wang

Fleuriel

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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159

141

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“…Enforced dimerization of RARa chimeric proteins appears to enhance its affinity for transcriptional corepressors such as Sin3A, SMRT and Nco-R as bona fide RARa fusion proteins generated in human leukemia (Lin and Evans, 2000;Minucci et al, 2000). Likewise, transcriptional repressor HIC1 (hypermethylated in cancer), which is a Kru¨ppel-like zinc-finger protein with an N-terminal BTB/POZ autonomous transcriptional repression domain, presumably requires dimerization through the BTB/POZ domain for the interaction with CtBP (Deltour et al, 2002). A similar mechanism to these two proteins may be active, in which homo-oligomerization of Evi-1a results in the efficient recruitment of CtBP.…”

Section: Discussionmentioning

confidence: 99%

Oligomerization of Evi-1 regulated by the PR domain contributes to recruitment of corepressor CtBP

et al. 2005

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Evi-1 is a transcription factor that is implicated in leukemic transformation of hematopoietic cells. Two distinct alternative forms, Evi-1a and Evi-1c, are generated from the EVI-1 gene. Whereas Evi-1a is widely recognized as an oncoprotein, a role for Evi-1c, which has an additional PR domain in the amino-terminus of Evi-1a, in leukemogenesis, has not been elucidated thus far. Aberrant oligomerization of transcription factors has recently emerged as a prevalent mechanism for activating their oncogenic potential in hematopoietic malignancies. Here, to study the mechanisms that underlie Evi-1-mediated oncogenesis, we investigated formation of oligomeric complexes by the Evi-1 proteins. We show that Evi-1a forms homo-oligomers, whereas Evi-1c exclusively exists as a monomer in mammalian cells. Remarkably, Evi-1c has lost the ability to interact with CtBP, a transcriptional corepressor that associates with Evi-1a. As a consequence, the ability of Evi-1c to repress transforming growth factor-b (TGF-b) signaling is significantly abrogated. These results identify a novel function of a PR domain to regulate oligomerization of transcription factors and suggest that homo-oligomerization may play a critical role in corepressor recruitment by the Evi-1 proteins. In addition, we found that the chimeric oncoprotein acute myelocytic leukemia (AML)1-Evi-1, generated in t(3;21) leukemia, also forms homo-oligomers and hetero-oligomers with Evi-1a, while it did not interact with Evi-1c. Consistent with the results, repression of TGF-b by AML1-Evi-1 was significantly enhanced by Evi-1a, whereas it was hardly affected by the presence of Evi-1c. These results suggest that oligomerization may contribute to the oncogenic potential of Evi-1-containing proteins.

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“…The CtBP family of proteins consists of evolutionarily conserved transcriptional corepressors (9). An increasing number of POZ-and ZF-containing transcription factors have been reported to use CtBP as their corepressors, including the human HIC1 and Drosophila Tramtrack 69 (Ttk69) proteins (11,43). We show that BCL6 can directly bind to human CtBP1 and recruit it to a number of BCL6 transcriptional targets including the promoter region of BCL6.…”

mentioning

confidence: 99%

CtBP Is an Essential Corepressor for BCL6 Autoregulation

Mendez¹,

Polo

Yu³

et al. 2008

Molecular and Cellular Biology

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The transcription repressor BCL6 plays an essential role in the formation and function of germinal centers (GCs). While normal B cells promptly shut off BCL6 when they exit the GC, many GC-derived B-cell lymphomas sustain BCL6 expression through chromosomal translocations and activating mutations. We have previously shown that a common effect of lymphoma-associated BCL6 gene alterations is to bypass a negative autoregulatory loop that controls its transcription. In this study, we report that BCL6 autoregulation is independent of several known corepressor complexes including silencing mediator for retinoid and thyroid hormone receptors, nuclear receptor coreceptor, BCL6 corepressor, and MTA3/NuRD. Furthermore, we show that BCL6 can interact with the CtBP (C-terminal binding protein) corepressor both in vitro and in vivo and that CtBP is recruited by BCL6 to its 5 regulatory region. In lymphoma cell lines carrying BCL6 translocations, small interfering RNA-mediated CtBP knock-down selectively relieved the previously silenced wild-type BCL6 allele but not the translocated alleles, which are driven by heterologous promoters. These results demonstrate that CtBP is a novel BCL6 corepressor and suggest that a unique corepressor requirement for BCL6 autoregulation may allow GC B cells to differentially control the expression of BCL6 and other BCL6 target genes in response to environmental stimuli during the GC stage of B cell development.BCL6 is a sequence-specific transcription repressor that is required for the formation of germinal centers (GC), and its deregulated expression underlies development of many GCderived B-cell lymphomas (12,44,47). Expression of BCL6 is developmentally regulated such that in the B-cell lineage, high levels of BCL6 are restricted to the GC stage. GC are dynamic and specialized structures in the secondary lymphoid organs within which B cells undergo immunoglobulin class switch recombination and somatic hypermutation to produce diverse, high-affinity antibodies (17,26). Widely considered to be the master regulator of the GC stage of B-cell development, BCL6 maintains the GC-specific gene expression program by silencing genes involved in B-cell activation (CD69, CD80, and NF-B1), response to DNA damage (TP53 and ATR), cell-cycle regulation (CCND2, CDKN1B, and CDKN1A), and plasma cell differentiation (PRDM1) (25,29,34,37,38,40,41). Thus, neither the memory nor the plasma cell differentiation program can be initiated until expression and activity of BCL6 are extinguished by GC exit signals.BCL6 is a 95-kDa phosphoprotein with six Krüppel-type zinc fingers (ZF) at the C terminus and an N-terminal POZ/BTB domain. Our earlier work demonstrated that the maximum repression activity of BCL6 requires the entire POZ/BTB domain as well as a separate middle region, repression domain II (RDII) (7). To date, a variety of BCL6 corepressors have been described. Among the corepressors with well-documented in vivo functions, nuclear receptor coreceptor (NCoR), silencing mediator for retinoid and thyroid hormon...

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The Human Candidate Tumor Suppressor Gene HIC1 Recruits CtBP through a Degenerate GLDLSKK Motif

Cited by 89 publications

References 58 publications

RETRACTED: Metabolic regulation of SIRT1 transcription via a HIC1:CtBP corepressor complex

RETRACTED: Metabolic regulation of SIRT1 transcription via a HIC1:CtBP corepressor complex

Oligomerization of Evi-1 regulated by the PR domain contributes to recruitment of corepressor CtBP

CtBP Is an Essential Corepressor for BCL6 Autoregulation

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