The TFIID subunit TAF4 regulates keratinocyte proliferation and has cell-autonomous and non-cell-autonomous tumour

Anas Fadloun1, Dominique Kobi, Jean-Christophe Pointud

  • 1Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 1 Rue Laurent Fries, 67404 Illkirch Cédex, France.

Development (Cambridge, England)
|July 13, 2007
PubMed

Insights

The TAF4 subunit is crucial for skin development and function. Its loss in mice causes neonatal death, fur loss, and promotes skin tumor development, revealing its role in keratinocyte proliferation and tumor suppression.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Dermatology

Background:

  • The TAF4 subunit of transcription factor TFIID plays a role in gene regulation.
  • Keratinocyte function is essential for skin barrier integrity and hair follicle cycling.

Purpose of the Study:

  • To investigate the function of TAF4 in mouse epidermis.
  • To determine the role of TAF4 in skin development, homeostasis, and tumor suppression.

Main Methods:

  • Conditional inactivation of the TAF4 gene in basal keratinocytes of foetal and adult mice.
  • Analysis of skin phenotype, gene expression, and tumor development.

Main Results:

  • TAF4 loss in foetal epidermis impairs skin barrier genes, causing neonatal lethality.
  • TAF4 inactivation in adult epidermis leads to fur loss, aberrant hair cycle, and epidermal hyperplasia.
  • TAF4 deficiency promotes malignant transformation of chemically induced skin tumors and melanocytic tumors.

Conclusions:

  • TAF4 is essential for regulating keratinocyte proliferation and maintaining skin homeostasis.
  • TAF4 exhibits both cell-autonomous and non-cell-autonomous tumor suppressor activities in the epidermis.

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...