Homeodomain transcription factor and tumor suppressor Prep1 is required to maintain genomic stability

Prep1 (pKnox1) is a homeodomain transcription factor of the TALE superclass whose members can act as co-factors of Hox. Prep1 is essential for embryogenesis, but in the adult it also acts as a tumor suppressor. We describe and analyze here the available mutant mice, their phenotypes and a few discordant cases. Moreover we specify the basic rules underlying the binding of Prep1 and its TALE partners to DNA, and their plasticity during embryonic development. We finally review recent data on Prep1 which indicate a very basic cellular function at the level of DNA replication and DNA damage.

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The homeodomain transcription factor Cdx1 reduces the growth of human colon cancer cells by reducing G1 Cdk kinase activity and cyclin D1 expression

Gastroenterology ◽

10.1016/s0016-5085(01)80687-9 ◽

2001 ◽

Vol 120 (5) ◽

pp. A139-A139

Author(s):

J LYNCH ◽

M KELLER ◽

E RANSUH ◽

P TRABER

Keyword(s):

Colon Cancer ◽

Transcription Factor ◽

Cyclin D1 ◽

Cancer Cells ◽

Kinase Activity ◽

Human Colon ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Homeodomain Transcription Factor ◽

Human Colon Cancer Cells

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Faculty Opinions recommendation of The Prrx1 homeodomain transcription factor plays a central role in pancreatic regeneration and carcinogenesis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717977054.793472398 ◽

2013 ◽

Author(s):

Arthur Mercurio

Keyword(s):

Transcription Factor ◽

Homeodomain Transcription Factor ◽

Pancreatic Regeneration

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Faculty Opinions recommendation of Disruption of the homeodomain transcription factor orthopedia homeobox (Otp) is associated with obesity and anxiety.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.731573073.793537403 ◽

2017 ◽

Author(s):

Joel Elmquist ◽

Kimberly Cox

Keyword(s):

Transcription Factor ◽

Homeodomain Transcription Factor

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A crucial role for the homeodomain transcription factor Hhex in lymphopoiesis

Blood ◽

10.1182/blood-2014-06-579813 ◽

2015 ◽

Vol 125 (5) ◽

pp. 803-814 ◽

Cited By ~ 23

Author(s):

Jacob T. Jackson ◽

Chayanica Nasa ◽

Wei Shi ◽

Nicholas D. Huntington ◽

Clifford W. Bogue ◽

...

Keyword(s):

Transcription Factor ◽

Crucial Role ◽

Homeodomain Transcription Factor ◽

Key Points

Key Points Hhex regulates development of diverse lymphoid lineages. Hhex regulates cycling of lymphoid precursors.

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The PDX1 Homeodomain Transcription Factor Negatively Regulates the Pancreatic Ductal Cell-specific Keratin 19 Promoter

Journal of Biological Chemistry ◽

10.1074/jbc.m605891200 ◽

2006 ◽

Vol 281 (50) ◽

pp. 38385-38395 ◽

Cited By ~ 25

Author(s):

Therese B. Deramaudt ◽

Mira M. Sachdeva ◽

Melanie P. Wescott ◽

Yuting Chen ◽

Doris A. Stoffers ◽

...

Keyword(s):

Transcription Factor ◽

Homeodomain Transcription Factor ◽

Keratin 19 ◽

Ductal Cell ◽

Pancreatic Ductal Cell

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ZIC1 Is a Putative Tumor Suppressor in Thyroid Cancer by Modulating Major Signaling Pathways and Transcription Factor FOXO3a

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2013-3729 ◽

2014 ◽

Vol 99 (7) ◽

pp. E1163-E1172 ◽

Cited By ~ 28

Author(s):

Wei Qiang ◽

Yuan Zhao ◽

Qi Yang ◽

Wei Liu ◽

Haixia Guan ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Transcription Factor ◽

Thyroid Cancer ◽

Tumor Suppressor ◽

Cancer Cells ◽

Colony Formation ◽

Promoter Hypermethylation ◽

Migration And Invasion ◽

Thyroid Cancer Cells

Context: ZIC1 has been reported to be overexpressed and plays an oncogenic role in some brain tumors, whereas it is inactivated by promoter hypermethylation and acts as a tumor suppressor in gastric and colorectal cancers. However, until now, its biological role in thyroid cancer remains totally unknown. Objectives: The aim of this study is to explore the biological functions and related molecular mechanism of ZIC1 in thyroid carcinogenesis. Setting and Design: Quantitative RT-PCR (qRT-PCR) was performed to evaluate mRNA expression of investigated genes. Methylation-specific PCR was used to analyze promoter methylation of the ZIC1 gene. The functions of ectopic ZIC1 expression in thyroid cancer cells were determined by cell proliferation and colony formation, cell cycle and apoptosis, as well as cell migration and invasion assays. Results: ZIC1 was frequently down-regulated by promoter hypermethylation in both primary thyroid cancer tissues and thyroid cancer cell lines. Moreover, our data showed that ZIC1 hypermethylation was significantly associated with lymph node metastasis in patients with papillary thyroid cancer. Notably, restoration of ZIC1 expression in thyroid cancer cells dramatically inhibited cell proliferation, colony formation, migration and invasion, and induced cell cycle arrest and apoptosis by blocking the activities of the phosphatidylinositol-3-kinase (PI3K)/Akt and RAS/RAF/MEK/ERK (MAPK) pathways, and enhancing FOXO3a transcriptional activity. Conclusions: Our data demonstrate that ZIC1 is frequently inactivated by promoter hypermethyaltion and functions as a tumor suppressor in thyroid cancer through modulating PI3K/Akt and MAPK signaling pathways and transcription factor FOXO3a.

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Inverse biological coupling between the bone-specific transcription factor Runx2 and the tumor suppressor P53 levels in osteosarcoma

Bone ◽

10.1016/j.bone.2012.02.168 ◽

2012 ◽

Vol 50 ◽

pp. S61 ◽

Cited By ~ 2

Author(s):

H. Taipaleenmaki⁎ ◽

M. Van der Deen ◽

Y. Zhang ◽

J.B. Lian ◽

J.L. Stein ◽

...

Keyword(s):

Transcription Factor ◽

Tumor Suppressor ◽

Tumor Suppressor P53 ◽

Specific Transcription Factor ◽

Biological Coupling

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BRN2 is a non-canonical melanoma tumor-suppressor

Nature Communications ◽

10.1038/s41467-021-23973-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Michael Hamm ◽

Pierre Sohier ◽

Valérie Petit ◽

Jérémy H. Raymond ◽

Véronique Delmas ◽

...

Keyword(s):

Transcription Factor ◽

Transcription Factors ◽

Tumor Suppressor ◽

The Other ◽

Pi3k Signaling ◽

Melanoma Tumor ◽

Temporal Regulation ◽

Metastatic Colonization ◽

Pou Domain

AbstractWhile the major drivers of melanoma initiation, including activation of NRAS/BRAF and loss of PTEN or CDKN2A, have been identified, the role of key transcription factors that impose altered transcriptional states in response to deregulated signaling is not well understood. The POU domain transcription factor BRN2 is a key regulator of melanoma invasion, yet its role in melanoma initiation remains unknown. Here, in a BrafV600EPtenF/+ context, we show that BRN2 haplo-insufficiency promotes melanoma initiation and metastasis. However, metastatic colonization is less efficient in the absence of Brn2. Mechanistically, BRN2 directly induces PTEN expression and in consequence represses PI3K signaling. Moreover, MITF, a BRN2 target, represses PTEN transcription. Collectively, our results suggest that on a PTEN heterozygous background somatic deletion of one BRN2 allele and temporal regulation of the other allele elicits melanoma initiation and progression.

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