Molecular Biology of the Skin. The Keratinocyte

297 Pages·1993·6.394 MB·English

by  Michael Darmon and Miroslav Blumenberg (Eds.)

Molecular
Biology Skin
The Keratinocyte
Edited by
Michel Darmon
Institut National de la Santé et de
la Recherche Médicale
Université de Nice
Parc Valrose
France
Miroslav Blumenberg
Department of Dermatology
New York University
New York, New York
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Front cover photograph: Morphological appearance of a DMBA/TPA-induced
mouse skin squamous cell carcinoma. See Chapter 2, Figure 16.
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Copyright © 1993 by ACADEMIC PRESS, INC.
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Library of Congress Cataloging-in-Publication Data
Molecular biology of the skin : the keratinocyte / edited by Michel
Darmon, M. Blumenberg.
p. cm.
Includes bibliographical references and index.
ISBN 0-12-203455-4
1. Skin—Molecular aspects. 2, Skin—Differentiation.
3. Keratinocytes. I. Darmon, Michel. II. Blumenberg, Miroslav Lj.
[DNLM: 1. Epidermis—cytology. 2. Keratinocytes—physiology.
3. Molecular Biology. WR 101 M718 1993]
QP88.5.M58 1993
612.7'9-dc20
DNLM/DLC
for Library of Congress
92-48406
CIP
PRINTED IN THE UNITED STATES OF AMERICA
93 94 95 96 97 98 Β C 9 8 7 6 5 4 3 2 1
Contributors
Numbers in parentheses indicate the pages on which the authors' contributions begin.
Bruno A. Bernard (207), L'OREAL, Centre de Recherche C. Zviak, 92583,
Clichy Cedex, France
Miroslav Blumenberg (1, 181), Ronald O. Perelman Department of Der­
matology and Department of Biochemistry, New York University Medical
Center, New York, New York 10016
Pascale Briand (245), Génétique et Pathologie Expérimentale, Institut Co­
chin de Génétique Moléculaire, CJF INSERM 90-03, F-75014, Paris,
France
Joseph M. Carroll (269), Department of Oral Biology and Pathology, School
of Dental Medicine, State University of New York at Stony Brook, Stony
Brook, New York 11794
Catherine Cavard (245), Génétique et Pathologie Expérimentale, Institut
Cochin de Génétique Moléculaire, CJF INSERM 90-03, F-75014, Paris,
France
Beverly A. Dale (79), Departments of Oral Biology, Periodontics, Biochemis­
try, and Medicine/Dermatology, University of Washington, Seattle, Wash­
ington 98195
Michel Darmon (181), Institut National de la Santé et de la Recherche
Médicale, Université de Nice, INSERM U 273, Parc Valrose, B.P. 71,
06108, Nice Cedex 2, France
Elizabeth S. Fenjves (269), Department of Oral Biology and Pathology,
School of Dental Medicine, State University of New York York at Stony
Brook, Stony Brook, New York 11794
Philip Fleckman (79), Department of Medicine/Dermatology, University of
Washington, Seattle, Washington 98195
Jonathan A. Garlick (269), Department of Oral Biology and Pathology,
School of Dental Medicine, State University of New York York at Stony
Brook, Stony Brook, New York 11794
ix
X Contributors
Daniel Hohl (151), Service de Dermatologie, Centre Hospitalier Univer­
sitaire Vaudois-Hôpital Beaumont, Lausanne, 1011 Switzerland
Ephraim Kam (79), Department of Oral Biology, University of Washington,
Seattle, Washington 98195
Serge Michel (107), Centre International de Recherches Dermatologiques
Galderma, (CIRD Galderma), F-06902 Sophia Antipolis, France
Richard B. Presland (79), Department of Oral Biology, University of Wash­
ington, Seattle, Washington 98195
Uwe Reichert (107), Centre International de Recherches Dermatologiques
Galderma, (CIRD Galderma), F-06902 Sophia Antipolis, France
Katheryn A. Resing (79), Department of Chemistry and Biochemistry, Uni­
versity of Colorado, Boulder, Colorado 80309
Dennis Roop (151), Departments of Dermatology and Cell Biology, Baylor
College of Medicine, Houston, Texas 77030
Rainer Schmidt (107), Centre International de Recherches Dermatologiques
Galderma, (CIRD Galderma), F-06902 Sophia Antipolis, France
Jurgen Schweizer (33), Research Program II, German Cancer Research Cen­
ter, D-6900 Heidelberg, Germany
Lome B. Taichman (269), Department of Oral Biology and Pathology,
School of Dental Medicine, State University of New York York at Stony
Brook, Stony Brook, New York 11794
Alain Zider (245), Génétique et Pathologie Expérimentale, Institut Cochin
de Génétique Moléculaire, CJF INSERM 90-03, F-75014, Paris, France
Foreword
By anatomical definition, the skin is a peripheral organ, and for genera­
tions of students and researchers it has also been a bit in the periphery of
general interest—both in basic research and in medicine. For the ambitious
biochemist and molecular biologist, the liver, for example, and the exocrine
pancreas were in the limelight of global attention. Research on the skin was
left to a small sect of specialists, dedicated afficionados, and dermatology
professors.
This view of the skin—and of the epidermis in particular—has changed
increasingly over the past two decades, and today the different kinds of cells
and the mechanisms that govern their differentiation and functions are of
central interest in general cell and molecular biology. Researchers studying
the molecular and genetic aspects of the skin and its diseases have been
recognized as pioneers of medical research. In recent years, results of skin
research have been discussed repeatedly in editorials of major journals in
science and medicine and have made it to the front pages and cover pictures.
Many individual advancements in methodology and molecular charac­
terization have contributed importantly to the growth and development of
skin research. For example, methods for culturing almost all cell types of
normal and diseased skin have developed, and even complex processes of cell
differentiation can now be studied in well-defined systems in vitro. More­
over, the keratinocytes of the epidermis and related epithelia have been both
a source and a research object in studies of diverse groups of cytoskeletal
molecules, from keratins to desmosomal proteins, not to mention the major
proteins associated with the terminal differentiation of epidermal cells and
the special molecules contributing to hair and nail formation. Research on
skin cells has also made significant contributions to the recognition of the
roles of growth factors, of oncogenes and tumor promoters, and of diverse
molecular defense mechanisms—from short protective peptides to true im­
mune responses.
Recently, for example, major autoantigenic molecules of certain blister­
ing autoimmune diseases of the skin have been identified and mutational
molecular defects have been associated with two forms of hereditary human
epidermolytic diseases.
xi
Xtt Foreword
In such exciting times of an exponential increase of molecular informa­
tion and insight into mechanisms, Molecular Biology of the Skin, which
brings together experts in different domains of basic research, is most timely
and topical. Consequently, the wide scope of chapters in this book also
reflects the development and differentiation of the field of skin research,
ranging from valuable reviews of the ever growing family of keratins and of
the genomic arrangements of their genes and pseudogenes (Chapters 1 and
2, by Blumenberg and Schweizer, respectively) to a most comprehensive and
detailed treatment of the major molecular components characteristic of ter­
minal differentiation of epidermal cells (Chapters 3, 4, and 5, by Dale et ai,
Hohl and Roop, and Reichert et al., respectively). An important principle in
the regulation of epithelial differentiation, that is, the control of the activities
of certain genes by retinoic acid, is presented in Chapter 6 by Darmon and
Blumenberg. The importance of studies using transgenic animals to under­
stand molecular functions and the development of skin diseases is summa­
rized in Chapter 8, by Cavard et al. A logical consequence of applicability,
the advantage of the skin and of the keratinocyte as its predominant cell type
as an obvious route for somatic gene therapy is outlined in an exciting
review from Lome Taichman's laboratory (Chapter 9, Carroll et al.). Finally,
as the development of molecular biology of the skin has been paralleled by
the research revealing the role of human papillomaviruses in the formation
of epithelial tumors, malignant carcinomas included, this group of viruses is
appropriately discussed in Chapter 7 by Bernard.
With rapid development of contemporary research, books summarizing
the evidence and knowledge accumulated are needed at certain well-chosen
intervals, for both the researchers and the broader community of scientists
and medical researchers. Clearly, Molecular Biology of the Skin appears at
the right time. And because of the breath-taking growth rate of scientific
information, authors of such reviews on "hot" research subjects must be not
only competent but also courageous. In this spirit, the present book is
doubtless a great service to the field of molecular research on the skin, and
authors as well as editors are to be congratulated for this accomplishment.
W. W. Franke
Preface
Skin plays protective (and esthetic) roles. In contrast to other organs, it
cannot be compared to a filter, a pump, a factory, or a computer. For this
reason the physiology and pathology of skin do not depend upon anatomi­
cal organization, but concern mainly basic cellular processes. For example,
the protective role of the epidermis stems directly from the terminal differen­
tiation of keratinocytes into corneocytes. As a result, a biologist willing to
study skin is obliged to address his or her questions directly in terms of
cellular and molecular biology. Despite the "simplicity" of skin as an organ,
dermatological diseases are paradoxically very complex: They affect cellular
pathways that are poorly understood and many of these diseases alter epi­
dermal differentiation itself. Thus, researchers in dermatology also address
their questions in the scope of molecular and cellular research. For example,
the extensive study of the biology of keratins in cultured cells, and in trans­
genic animals has led to the information necessary to unravel the molecular
basis of several human genetic skin disorders.
The use of a common language by dermatologists and molecular biolo­
gists is obvious when one attends scientific meetings or reads journals,
whether specialized in dermatology or of wider scope. But a book emphasiz­
ing this harmony of ideas and reviewing essential topics about the molecular
biology of the keratinocyte for both the medical and the scientific commu­
nities was still lacking. We hope that this book will play this role. The time is
particularly appropriate for this volume because the studies from several
divergent areas, as described here, converge to create a critical mass that
will, we are certain, attract a large number of dermatologists to basic and
clinical research.
We hope that this book will be useful not only for people interested in
dermatology but also for people with wider interests, such as developmental
biologists, because keratinization represents a prototype of terminal differ­
entiation and also offers a very attractive model for the study of retinoids;
surgeons and gene therapists, because human keratinocytes, unlike most cell
types, can be grown in vitro for many generations without losing their
normal phenotype and thus can reform in vitro a functional epidermis,
which can be grafted back to patients; virologists, because human pa-
xiii
XW Preface
pillomaviruses and other viruses whose target is exclusively the keratinocyte
still represent a major medical challenge; and, finally, pharmacologists, be­
cause effective drugs without dangerous side effects are still expected in
dermatology.
Michel Darmon and Miroslav Blumenberg
1
Molecular Biology of Human
Keratin Genes
Miroslav Blumenberg
Introduction
Gene Structure
Protein Sequences
Mapping of Keratin Genes
Evolution
Intron-Exon Boundaries
Central Domains
Terminal Domains
Mutations
Polymorphism
Deleterious Mutations
Regulation of Keratin Expression
Mutual Costabilization
Regulation of Transcription
The Role of DNA Methylation
Nuclear Transcription Factors
General Transcriptions Factors
Specific Elements
The Modulators
The Specific Case of K8 and Kl 8 Genes
Keratin Expression in Xenopus laevis
Perspectives
References
Introduction
Ten years have passed since the pioneering reports of cloning and sequencing
of human keratin genes (Hanukoglu and Fuchs, 1982). Murine, bovine, and
ovine genes soon followed (Steinert et al., 1983; Jorcano et al., 1984; Powell
et al., 1986), heralding an unabating stream of keratin gene sequences. Of
the 19 keratins described in the Moll catalog (Moll et al., 1982), all but one
Molecular Biology of the Skin: The Keratinocyte
Copyright © 1993 by Academic Press, Inc. All rights of reproduction in any form reserved. 1
2 M. Blumenberg
TABLE 1 Keratin Sequence Determinations
Keratin Reference source
Κ 1 Johnson et ai, 1985
Steinert et al, 1985 (Mouse)
Κ 2 Not available
Κ 3 Klinge et al, 1987
Κ 4 Hanukoglu and Fuchs, 1983
Leube et al, 1988
Knapp et al, 1986 (Mouse)
Κ 5 Lersch and Fuchs, 1988
Κ 6 Tyner et al, 1985
Κ 7 Glass et al, 1985
Κ 8 Glass and Fuchs, 1988
Leube et al, 1988
Yamamoto et al, 1990
Krauss and Franke, 1990
Oullet et al, 1988 (Mouse)
Tamai et al, 1991
Hsieh et al, 1992 (Rat)
Franz and Franke, 1986 (Toad)
Giordano et al, 1990 (Goldfish)
Κ 9 N.A.
Κ 10 Darmon et al, 1987
Zhou et al, 1988
Steinert et al, 1983 (Mouse)
Rieger et al, 1985 (Bovine)
Κ 11 Mischke and Wild, 1987 Allelic variant of Κ 10
Κ 12 N.A.
Κ 13 Kuruceitf/., 1989
Mischke et al, 1989
Winter et al, 1990 (Mouse)
Κ 14 Hanukoglu and Fuchs, 1982
Marchuk et al, 1985
Knapp et al, 1987 (Mouse)
Κ 15 Bader et al, 1988
Leube et al, 1988
Κ 16 RayChaudhury et al, 1986*
Κ 17 Savtchenko et al, 1990^
Knapp et al, 1987 (Mouse)
Κ 18 Kulesh and Oshima, 1989
Oshima et al, 1986
Romano et al, 1986
Ichinose et al, 1988 (Mouse)
Κ 19 Stasiak and Lane, 1987
Bader et al, 1988
Bader et al, 1986 (Bovine)
Κ 20 W. W. Franke, 1991 pers. corn.
Κ 21 Chandler et al, 1991 (Rat)
KHal Bertolino et al, 1988 (Murine)
KHa2 Bertolino et al, 1990 (Murine)
Wilson et al, 1988 (Ovine)
{continued)