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Cited by 58Developmental Biology and Gene RegulationGenomics and Chromatin DynamicsBioinformatics and Genomic Networks

Diverse functional networks of Tbx3 in development and disease

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Washkowitz, Andrew J., Gavrilov, Svetlana, Begum, Salma, Papaioannou, Virginia E.·2012·WIREs Systems Biology and Medicine
DOI 10.1002/wsbm.1162PMC PMC3328642
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Abstract

The T‐box transcription factor Tbx3 plays multiple roles in normal development and disease. In order to function in different tissues and on different target genes, Tbx3 binds transcription factors or other cofactors specific to temporal or spatial locations. Examining the development of the mammary gland, limbs, and heart as well as the biology of stem cells and cancer provides insights into the diverse and common functions that Tbx3 can perform. By either repressing or activating transcription of target genes in a context‐dependent manner, Tbx3 is able to modulate differentiation of immature progenitor cells, control the rate of cell proliferation, and mediate cellular signaling pathways. Because the direct regulators of these cellular processes are highly context‐dependent, it is essential that Tbx3 has the flexibility to regulate transcription of a large group of targets, but only become a active on a small cohort of them at any given time or place. Moreover, Tbx3 must be responsive to the variety of different upstream factors that are present in different tissues. Only by understanding the network of genes, proteins, and molecules with which Tbx3 interacts can we hope to understand the role that Tbx3 plays in normal development and how its aberrant expression can lead to disease. Because of its myriad functions in disparate developmental and disease contexts, Tbx3 is an ideal candidate for a systems‐based approach to genetic function and interaction. WIREs Syst Biol Med 2012. doi: 10.1002/wsbm.1162 This article is categorized under: Developmental Biology > Developmental Processes in Health and Disease Developmental Biology > Stem Cell Biology and Regeneration

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  • TBX3 functions predominantly as a transcriptional repressor.

    “TBX3 functions predominantly as a transcriptional repressor.”

    From The oncoprotein TBX3 is controlling severity in experimental arthritis (2019) · cites this paper as [18]

    The Conclusion (page unavailable) describes a transcriptional repression module, and the cancer section gives examples of genes TBX3 represses. But the Abstract and Conclusion also say TBX3 can activate transcription depending on context; the paper does not establish that repression is its predominant function. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Both TBX3 and TBX5 are involved in bone development and remodeling.

    “Among other functions, both proteins are involved in bone development [18–20] and remodeling [21].”

    From The oncoprotein TBX3 is controlling severity in experimental arthritis (2019) · cites this paper as [18]

    The 'Tbx3 in limb development' section reports that Tbx3-null mice have missing or abnormal forelimb elements, supporting a role for TBX3 in skeletal development. Our copy does not establish a comparable role for TBX5 or address bone remodeling; its reference to remodeling concerns the heart. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Tissue-specific regulation of Tbx3 has been previously documented in mice and humans.

    “This can be explained by tissue-specific regulation of Tbx3 that has been previously documented in mice [18] and humans [18, 25].”

    From The oncoprotein TBX3 is controlling severity in experimental arthritis (2019) · cites this paper as [18]

    The Abstract (page not available) describes Tbx3 expression in specific mouse tissues, and the limb-development section describes spatial regulation of that expression. The paper also reports tissue-specific effects of human TBX3 mutations, but those effects do not establish tissue-specific regulation of TBX3 in humans. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Tbx3 expression within lung mesenchyme at E14.5 is markedly abolished in Usp15null mutants.

    “Tbx3 expression within lung mesenchyme at E14.5 was also markedly abolished from Usp15null mutants49,50 (Fig. 6c).”

    From Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis (2024) · cites this paper as [50]

    The Abstract (page unavailable) says Tbx3 is expressed in developing lungs, but it does not address lung mesenchyme at E14.5 or Usp15-null mutants. Searches for Usp15, E14.5 lung, and lung mesenchyme found no passage reporting the claimed loss of expression. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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Authors
Washkowitz, A. J., Gavrilov, S., Begum, S., & Papaioannou, V. E.
Affiliations
Columbia University Irving Medical Center (US)
Corresponding author
Papaioannou, Virginia E.
ORCID
Venue
WIREs Systems Biology and Medicine
Publisher
Wiley
Published
2012-02-14
Volume
4
Issue
3
Pages
273-283
ISSN
  • 1939-005X (ISSN-L)
  • 1939-5094
DOI
10.1002/wsbm.1162
PMC
PMC3328642
OpenAlex
W2058780123
Cited by
58
References
8
Citations by year
2026: 1 · 2025: 1 · 2024: 5 · 2023: 6 · 2022: 4 · 2021: 2 · 2020: 2 · 2019: 8 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 4 · 2014: 6 · 2013: 4 · 2012: 4
FWCI
2.32
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • WIREs Systems Biology and Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R37HD033082)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
Keywords
TBX3, T-box transcription factor, transcriptional regulation, protein-protein interaction, mammary gland development, limb development, heart development, stem cells, cancer, cell proliferation, cell differentiation, developmental disorders
MeSH terms
Abnormalities, Multiple, Animals, Breast Diseases, Extremities, Heart, Humans, Mutation, Myocardium, Neoplasms, Stem Cells, Ulna, T-Box Domain Proteins, Mammary Glands, Human

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