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Up-regulation of p21WAF1/CIP1 in psoriasis and after the application of irritants and tape stripping

Up-regulation of p21WAF1/CIP1 in psoriasis and after the application of irritants and tape stripping
Up-regulation of p21WAF1/CIP1 in psoriasis and after the application of irritants and tape stripping
p21WAF1/CIP1 is a nucleoprotein that was initially characterized by its ability to be regulated transcriptionally by p53 and by its ability to mediate growth arrest by binding to cyclin-dependent kinases. Although p21WAF1/CIP1 is thought to mediate the effects of p53 in causing growth arrest, p21WAF1/CIP1 is also regulated in a p53-independent manner, e.g., during terminal differentiation of some cell lines. Growth factors including epidermal growth factor also induce p21WAF1/CIP1 through p53-independent pathways. Because the epidermal growth factor signaling pathway is abnormal in psoriatic epidermis, we studied p21WAF1/CIP1 expression, using in situ hybridization and immunohistochemistry, in psoriasis. Both p21WAF1/CIP1 mRNA and protein were significantly elevated in untreated psoriatic plaques compared with uninvolved psoriatic skin (p < 0.0001), with the up-regulation of p21WAF1/CIP1 being predominantly suprabasal. This increase was accompanied by a small increase in p53 protein expression of uncertain significance. Furthermore, p21WAF1/CIP1 expression was induced in skin after sellotape stripping and by the application of agents, such as dithranol, that are capable of inducing hyperproliferation. The pattern of p21WAF1/CIP1 expression observed is consistent with a role in induction and maintenance of differentiation. Our experiments, however, cannot determine whether the abnormalities of p21WAF1/CIP1 epidermal expression in psoriasis and after insult are independent of changes in p53 expression.
differentiation, dithranol, p53, proliferation
0022-202X
274-279
Healy, Eugene
400fc04d-f81a-474a-ae25-7ff894be0ebd
Reynolds, Nicholas J.
ebef3e44-f65b-4598-a259-29ac74ae63ea
Smith, Martin D.
871dbd2f-83bb-4c7e-ab1d-c890394db215
Harrison, David
864be260-5888-46c3-a883-c683bd9bcc98
Doherty, Elaine
05bae711-45d8-4d4e-b7e8-5a6b2aec93db
Campbell, Christine
c8f4379f-2263-4099-a8f4-6c796c26bba3
Rees, Jonathan L.
8a58a967-d239-4300-b363-ca471bf7047f
Healy, Eugene
400fc04d-f81a-474a-ae25-7ff894be0ebd
Reynolds, Nicholas J.
ebef3e44-f65b-4598-a259-29ac74ae63ea
Smith, Martin D.
871dbd2f-83bb-4c7e-ab1d-c890394db215
Harrison, David
864be260-5888-46c3-a883-c683bd9bcc98
Doherty, Elaine
05bae711-45d8-4d4e-b7e8-5a6b2aec93db
Campbell, Christine
c8f4379f-2263-4099-a8f4-6c796c26bba3
Rees, Jonathan L.
8a58a967-d239-4300-b363-ca471bf7047f

Healy, Eugene, Reynolds, Nicholas J., Smith, Martin D., Harrison, David, Doherty, Elaine, Campbell, Christine and Rees, Jonathan L. (1995) Up-regulation of p21WAF1/CIP1 in psoriasis and after the application of irritants and tape stripping. Journal of Investigative Dermatology, 105 (2), 274-279. (doi:10.1111/1523-1747.ep12318430). (PMID:7636313)

Record type: Article

Abstract

p21WAF1/CIP1 is a nucleoprotein that was initially characterized by its ability to be regulated transcriptionally by p53 and by its ability to mediate growth arrest by binding to cyclin-dependent kinases. Although p21WAF1/CIP1 is thought to mediate the effects of p53 in causing growth arrest, p21WAF1/CIP1 is also regulated in a p53-independent manner, e.g., during terminal differentiation of some cell lines. Growth factors including epidermal growth factor also induce p21WAF1/CIP1 through p53-independent pathways. Because the epidermal growth factor signaling pathway is abnormal in psoriatic epidermis, we studied p21WAF1/CIP1 expression, using in situ hybridization and immunohistochemistry, in psoriasis. Both p21WAF1/CIP1 mRNA and protein were significantly elevated in untreated psoriatic plaques compared with uninvolved psoriatic skin (p < 0.0001), with the up-regulation of p21WAF1/CIP1 being predominantly suprabasal. This increase was accompanied by a small increase in p53 protein expression of uncertain significance. Furthermore, p21WAF1/CIP1 expression was induced in skin after sellotape stripping and by the application of agents, such as dithranol, that are capable of inducing hyperproliferation. The pattern of p21WAF1/CIP1 expression observed is consistent with a role in induction and maintenance of differentiation. Our experiments, however, cannot determine whether the abnormalities of p21WAF1/CIP1 epidermal expression in psoriasis and after insult are independent of changes in p53 expression.

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More information

Published date: August 1995
Keywords: differentiation, dithranol, p53, proliferation
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 334170
URI: https://eprints.soton.ac.uk/id/eprint/334170
ISSN: 0022-202X
PURE UUID: e0be4252-b0c4-4b5d-8e42-5ca263f81857

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Date deposited: 14 Mar 2012 14:01
Last modified: 18 Jul 2017 06:12

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