The epidermis: rising to the surface

Fuchs, Elaine; Byrne, Carolyn

doi:10.1016/0959-437x(94)90140-x

Cited by 216 publications

(208 citation statements)

References 65 publications

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“…When proliferating basal cells detach from the basement membrane they produce the di erentiation cytoskeleton and subsequently, the corni®ed envelope (Fuchs and Byrne, 1994). Our model is that this new cytoskeleton might be too rigid and create a physical constraint that would prevent the cell from splitting up even when the DNA replication machinery is still functional.…”

Section: Mechanisms Of Keratinocyte Endoreplication and C-myc Functionmentioning

confidence: 99%

“…Within the basal layer continuous proliferation throughout adult life accounts for the loss of cells that shed as squames from the surface of skin (Watt, 1989;Fuchs and Byrne, 1994). A constant balance between both processes is crucial to maintain the normal structure of epidermis and its alteration results in skin diseases.…”

Section: Introductionmentioning

confidence: 99%

“…As keratinocytes cease proliferation and migrate into the suprabasal layers they switch from a cytoskeleton formed by keratins K5 and K14 to another one formed by keratins K1 and K10. Concomitantly, they enlarge and initiate the expression of precursors and other components of the corni®ed envelope, such as involucrin, loricrin and ®laggrin (Watt and Green, 1981;Fuchs and Byrne, 1994).…”

Section: Introductionmentioning

confidence: 99%

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Normal and c-Myc-promoted human keratinocyte differentiation both occur via a novel cell cycle involving cellular growth and endoreplication

2000

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The relationship between cell cycle and di erentiation in human keratinocytes is poorly understood. It is believed that keratinocytes suppress DNA replication and cell cycle arrest in G0 before they initiate terminal di erentiation. However, a temporal separation between both events has not been established. Moreover, c-Myc promotes keratinocyte di erentiation without causing cell cycle arrest. To address these paradoxes we have analysed cell cycle control during normal and c-Mycpromoted di erentiation. Continuous activation of c-Myc or initiation of terminal di erentiation results in a block of G2/M, cellular growth, endoreplication and polyploidy. Keratinocytes abandon G1, continue replicating DNA as they di erentiate terminally and become polyploid. In fact, simply blocking mitosis with nocodazole resulted in increased cell size, terminal di erentiation and endoreplication. This indicates that terminal di erentiation associates with defective cell cycle progression and provides a novel insight into c-Myc biology.

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Section: Mechanisms Of Keratinocyte Endoreplication and C-myc Functionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Normal and c-Myc-promoted human keratinocyte differentiation both occur via a novel cell cycle involving cellular growth and endoreplication

2000

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“…This process is characterized by step-wise changes in cellular morphology, communication potential, loss of cellular organelles, withdrawal from the cell cycle and both the induction and suppression of gene expression (reviewed by Yuspa 1994;Fuchs and Byrne 1994;Watt and Jones 1993). The transcriptional events that control the di erentiation process in epidermal cells have not been well-de®ned.…”

Section: Introductionmentioning

confidence: 99%

CRE DNA binding proteins bind to the AP-1 target sequence and suppress AP-1 transcriptional activity in mouse keratinocytes

et al. 1999

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Previously, we have shown that nuclear extracts from cultured mouse keratinocytes induced to di erentiate by increasing the levels of extra-cellular calcium contain Fra-1, Fra-2, Jun B, Jun D and c-Jun proteins that bind to the AP-1 DNA binding sequence. Despite this DNA binding activity, AP-1 reporter activity was suppressed in these cells. Here, we have detected the CREB family proteins CREB and CREMa as additional participants in the AP-1 DNA binding complex in di erentiating keratinocytes. AP-1 and CRE DNA binding activity correlated with the induction of CREB, CREMa and ATF-1 and CREB phosphorylation at ser 133 (ser 133 phospho-CREB) in the transition from basal to di erentiating keratinocytes, but the activity of a CRE reporter remained unchanged. In contrast, the CRE reporter was activated in the presence of the dominantnegative (DN) CREB mutants, KCREB and A-CREB, proteins that dimerize with CREB family members and block their ability to bind to DNA. The increase in CRE reporter activity in the presence of these mutants suggests that CRE-mediated transcriptional activity is suppressed in keratinocytes through protein-protein interactions involving a factor that dimerizes with the CREB leucine zipper. In experiments where the A-CREB mutant was co-transfected with an AP-1 reporter construct, transcriptional activity was also increased indicating that a CREB family member binds AP-1 sites and represses AP-1 transcriptional activity as well. Exogenous expression of the transcriptional repressor CREMa down-regulated both CRE and AP-1 reporters in keratinocytes suggesting that this factor may contribute to the suppression of AP-1 transcriptional activity observed in di erentiating keratinocytes.

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“…This response is sensitive to a perturbation of the cellular redox equilibrium. It is known that many promoters that are active in terminally differentiating epidermal cells contain functionally important AP-1 sites [28]. In this regard, the protective or degenerative role played by the UV-A induced activation of AP-1 in skin cells deserves further investigation.…”

mentioning

confidence: 99%