Terminal differentiation in keratinocytes involves positive as well as negative regulation by retinoic acid receptors and retinoid X receptors at retinoid response elements

1992 ◽  
Vol 12 (11) ◽  
pp. 4862-4871
Author(s):  
B J Aneskievich ◽  
E Fuchs
Keyword(s):  
Retinoic Acid ◽  
Terminal Differentiation ◽  
Cell Types ◽  
Epidermal Differentiation ◽  
Retinoic Acid Receptors ◽  
Keratinocyte Differentiation ◽  
Epidermal Keratinocytes ◽  
Retinoid X Receptors ◽  
Response Elements ◽  
X Receptors

Terminal differentiation of epidermal keratinocytes is inhibited by 1 microM retinoic acid, a concentration which induces differentiation in a number of cell types, including F9 teratocarcinoma cells. The molecular basis for these opposing retinoid responses is unknown, although retinoic acid receptors (RARs) and retinoid X receptors (RXRs) have been detected in both cell types. When F9 cells are stably transfected with a truncated RAR alpha lacking the E/F domain necessary for ligand binding and RAR/RXR dimerization, action at retinoid response elements is suppressed and cells produce a retinoic acid-resistant phenotype; i.e., they are blocked in differentiation (A. S. Espeseth, S. P. Murphy, and E. Linney, Genes Dev. 3:1647-1656, 1989). If retinoid receptors influence epidermal differentiation only in a negative fashion, then suppression of transactivation at retinoid response elements would be expected to enhance, rather than block, keratinocyte differentiation. In this study, we show that surprisingly, even though constitutive expression of an analogous truncated RAR gamma in keratinocytes specifically suppressed transactivation at retinoid response elements, keratinocytes were blocked, rather than enhanced, in their ability to undergo morphological and biochemical features of differentiation. These findings demonstrate a direct and hitherto unrecognized role for RARs and RXRs in positively as well as negatively regulating epidermal differentiation. Additionally, our studies extend those of Espeseth et al. (Genes Dev. 3:1647-1656, 1989), indicating a novel RAR function independent of the E/F domain.

scholarly journals Terminal differentiation in keratinocytes involves positive as well as negative regulation by retinoic acid receptors and retinoid X receptors at retinoid response elements.

1992 ◽  
Vol 12 (11) ◽  
pp. 4862-4871 ◽  
Author(s):  
B J Aneskievich ◽  
E Fuchs
Keyword(s):  
Retinoic Acid ◽  
Terminal Differentiation ◽  
Cell Types ◽  
Epidermal Differentiation ◽  
Retinoic Acid Receptors ◽  
Keratinocyte Differentiation ◽  
Epidermal Keratinocytes ◽  
Retinoid X Receptors ◽  
Response Elements ◽  
X Receptors

Terminal differentiation of epidermal keratinocytes is inhibited by 1 microM retinoic acid, a concentration which induces differentiation in a number of cell types, including F9 teratocarcinoma cells. The molecular basis for these opposing retinoid responses is unknown, although retinoic acid receptors (RARs) and retinoid X receptors (RXRs) have been detected in both cell types. When F9 cells are stably transfected with a truncated RAR alpha lacking the E/F domain necessary for ligand binding and RAR/RXR dimerization, action at retinoid response elements is suppressed and cells produce a retinoic acid-resistant phenotype; i.e., they are blocked in differentiation (A. S. Espeseth, S. P. Murphy, and E. Linney, Genes Dev. 3:1647-1656, 1989). If retinoid receptors influence epidermal differentiation only in a negative fashion, then suppression of transactivation at retinoid response elements would be expected to enhance, rather than block, keratinocyte differentiation. In this study, we show that surprisingly, even though constitutive expression of an analogous truncated RAR gamma in keratinocytes specifically suppressed transactivation at retinoid response elements, keratinocytes were blocked, rather than enhanced, in their ability to undergo morphological and biochemical features of differentiation. These findings demonstrate a direct and hitherto unrecognized role for RARs and RXRs in positively as well as negatively regulating epidermal differentiation. Additionally, our studies extend those of Espeseth et al. (Genes Dev. 3:1647-1656, 1989), indicating a novel RAR function independent of the E/F domain.

scholarly journals Multiple retinoid-responsive receptors in a single cell: families of retinoid "X" receptors and retinoic acid receptors in the Xenopus egg.

1992 ◽  
Vol 89 (6) ◽  
pp. 2321-2325 ◽  
Author(s):  
B. Blumberg ◽  
D. J. Mangelsdorf ◽  
J. A. Dyck ◽  
D. A. Bittner ◽  
R. M. Evans ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Single Cell ◽  
Retinoic Acid Receptors ◽  
Retinoid X Receptors ◽  
Xenopus Egg ◽  
X Receptors

Retinoic acid receptors and retinoid X receptors in the mature retina: Subtype determination and cellular distribution

1999 ◽  
Vol 19 (4) ◽  
pp. 338-347 ◽  
Author(s):  
Jacques J.M. Janssen ◽  
Eleonoor D. Kuhlmann ◽  
Anke H.M. van Vugt ◽  
Huub J. Winkens ◽  
Bert P.M. Janssen ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptors ◽  
Cellular Distribution ◽  
Retinoid X Receptors ◽  
X Receptors

Retinoid receptors promote primary neurogenesis in Xenopus

Development ◽  
1997 ◽  
Vol 124 (2) ◽  
pp. 515-523 ◽  
Author(s):  
C.R. Sharpe ◽  
K. Goldstone
Keyword(s):  
Retinoic Acid ◽  
Nuclear Hormone Receptor ◽  
Retinoic Acid Receptors ◽  
Primary Neurons ◽  
Retinoid X Receptors ◽  
Over Expression ◽  
Retinoid Receptors ◽  
X Receptors ◽  
Synthetic Mrna ◽  
Primary Neurogenesis

Retinoid receptors, which are members of the nuclear hormone receptor superfamily, act as ligand-dependent transcription factors. They mediate the effects of retinoic acid primarily as heterodimers of retinoic acid receptors (RARs) and retinoid X receptors (RXRs). To analyse their function, xRXR beta synthetic mRNA was injected into Xenopus embryos in combination with normal and mutated xRAR alpha transcripts. Two informative phenotypes are reported here. Firstly, over-expression of xRXR beta with xRAR alpha results in the formation of ectopic primary neurons. Secondly, blocking retinoid signalling with a mutated xRAR alpha results in a lack of primary neurons. These two phenotypes, from contra-acting manipulations, indicate a role for retinoid signalling during neurogenesis.

Response element selectivity for heterodimerization of vitamin D receptors with retinoic acid and retinoid X receptors

1994 ◽  
Vol 12 (3) ◽  
pp. 327-339 ◽  
Author(s):  
M Schräder ◽  
K M Müller ◽  
M Becker-André ◽  
C Carlberg
Keyword(s):  
Vitamin D ◽  
Retinoic Acid ◽  
Specific Response ◽  
Direct Repeats ◽  
Response Element ◽  
Retinoid X Receptors ◽  
Response Elements ◽  
Vitamin D Receptors ◽  
Receptor Complexes ◽  
X Receptors

ABSTRACT The transcription of vitamin D (VD) responsive genes is regulated by three different nuclear signalling pathways mediated by homodimers of VD receptors (VDRs), heterodimers of VDRs and retinoid X receptors (RXRs) and heterodimers of VDRs with retinoic acid receptors (RARs). Here, the in vitro DNA-binding affinity of all three receptor complexes was shown to be enhanced by the presence of VD. However, the specificity of the three pathways was dictated by the differential affinities of the receptor complexes for VD response elements. Potential response elements were distinguished by the sequence, the separation and the relative orientation of the hexameric core binding motifs. It was found that both VDR-RAR and VDR-RXR heterodimers act functionally on all three response element configurations: direct repeats, palindromes and inverted palindromes. With direct repeats, neither heterodimer type showed a preference for any of the three principal core motifs, (A/G)GGTGA, (A/G)GGTCA and (A/G)GTTCA. However, while they did exhibit preferences for core motifs in palindromes, the spacing requirements were identical for both complexes. Inverted palindromes, however, formed the most specific response elements. A simple model explains a steric link between the optimal spacing of direct repeats and that of inverted palindromes. Taken together, the experimental data and the model provide further criteria for the screening of VD responsive genes.

scholarly journals The role of cathepsin E in terminal differentiation of keratinocytes

2011 ◽  
Vol 392 (6) ◽  
Author(s):  
Tomoyo Kawakubo ◽  
Atsushi Yasukochi ◽  
Kuniaki Okamoto ◽  
Yoshiko Okamoto ◽  
Seiji Nakamura ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Primary Cultures ◽  
Terminal Differentiation ◽  
Epidermal Differentiation ◽  
Keratinocyte Differentiation ◽  
Epidermal Keratinocytes ◽  
Marker Genes ◽  
Differentiation Markers ◽  
Cathepsin E

Abstract Cathepsin E (CatE) is predominantly expressed in the rapidly regenerating gastric mucosal cells and epidermal keratinocytes, in addition to the immune system cells. However, the role of CatE in these cells remains unclear. Here we report a crucial role of CatE in keratinocyte terminal differentiation. CatE deficiency in mice induces abnormal keratinocyte differentiation in the epidermis and hair follicle, characterized by the significant expansion of corium and the reduction of subcutaneous tissue and hair follicle. In a model of skin papillomas formed in three different genotypes of syngeneic mice, CatE deficiency results in significantly reduced expression and altered localization of the keratinocyte differentiation induced proteins, keratin 1 and loricrin. Involvement of CatE in the regulation of the expression of epidermal differentiation specific proteins was corroborated by in vitro studies with primary cultures of keratinocytes from the three different genotypes of mice. In wild-type keratinocytes after differentiation inducing stimuli, the CatE expression profile was compatible to those of the terminal differentiation marker genes tested. Overexpression of CatE in mice enhances the keratinocyte terminal differentiation process, whereas CatE deficiency results in delayed differentiation accompanying the reduced expression or the ectopic localization of the differentiation markers. Our findings suggest that in keratinocytes CatE is functionally linked to the expression of terminal differentiation markers, thereby regulating epidermis formation and homeostasis.

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