Summary
The epidermis is a tissue that undergoes a very complex and tightly controlled differentiation program. The elaboration of this program is generally flawless, resulting in the production of an effective protective barrier for the organism. Many of the genes expressed during keratinocyte differentiation are expressed in a coordinate manner; this suggests that common regulatory models may emerge. The simplest model envisions a ‘common regulatory element’ that is possessed by all genes that are regulated together (e.g., involucrin and transglutaminase type 1). Studies to date, however, have not identified any such elements and, if anything, the available studies suggest that appropriate expression of each gene is achieved using sometime subtly and sometime grossly different mechanisms.
Recent studies indicate that a variety of transcription factors (AP1, AP2, POU domain, Sp1, STAT factors) are expressed in the epidermis and, in many cases, multiple members of several families are present (e.g., AP1 and POU domain factors). The simultaneous expression of multiple members of a single transcription factor family provides numerous opportunities for complex regulation. Some studies suggest that specific members of these families interact with specific keratinocyte genes. The best studied of these families in epidermis is the AP1 family of factors. All of the known AP1 factors are expressed in epidermis [52] and each is expressed in a specific spatial pattern that suggests the potential to regulate multiple genes. It will be important to determine the role of each of these members in regulating keratinocyte gene expression.
Finally, information is beginning to emerge regarding signal transduction in keratinocytes. Some of the early events in signal transduction have been identified (e.g., PLC and PKC activation, etc.) and some of the molecular targets of these pathways (e.g., AP1 transcription factors) are beginning to be identified. Eventually we can expect to elucidation of all of the steps between the interaction of the stimulating agent with its receptor and the activation of target gene expression.
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References
EckertRL (1989) Physiol. Rev. 69: 1316–1346
GreenH (1977) Cell 11: 405–416
GreenH, FuchsE, & WattF (1982) Cold Spring Harb. Symp. Quant. Biol. 46: 293–301
LavkerRM, MillerSJ, & SunTT (1993) Recent Results Cancer Res. 128: 31–43
YangJS, LavkerRM, & SunTT (1993) J. Invest. Dermatol. 101: 652–659
HolbrookKA & WolffK (1987) In: FitzpatrickTB, LesenAZ, WolffK, FreedbergIM, & AustenKF (Eds) Dermatology in General Medicine (pp. 93–131) McGraw Hill, New York
EliasPM, MenonGK, GraysonS, & BrownBE (1988) J. Invest. Dermatol. 91: 3–10
StevenAC, BisherME, RoopDR, & SteinertPM (1990) J. Struct. Biol. 104: 150–162
TakashashiM, TezukaT, & KatunumaN (1992) FEBS Lett. 308: 79–82
MatoltsyAG & MatoltsyMN (1966) J. Invest. Dermatol. 46: 127–129
RiceRH & GreenH (1977) Cell 11: 417–422
AbernathyJL, HillRL, & GoldsmithLA (1977) J. Biol. Chem. 252: 1837–1839
PolakowskaR, HertingE, & GoldsmithLA (1991) J. Invest. Dermatol. 96: 285–288
ThacherSM & RiceRH (1985) Cell 40: 685–695
FuchsE (1990) J. Cell Biol. 111: 2807–2814
RoopDR, HuitfeldtH, KilkennyA, & YuspaSH (1987) Differentiation 35: 143–150
StolerA, KopanR, DuvicM, & FuchsE (1988) J. Cell Biol. 107: 427–446
YuspaSH (1994) Cancer Res. 54: 1178–1189
SteinertPM, StevenAC, & RoopDR (1985) Cell 42: 411–420
AlbersK, & FuchsE (1992) Int. Rev. Cytol. 134: 243–279
Woodcock-MitchellJ, EichnerR, NelsonWG, & SunTT (1982) J. Cell Biol. 95: 580–588
HatzfeldM & WeberK (1990) J. Cell Biol. 110: 1199–1210
CoulombePA & FuchsE (1990) J. Cell Biol. 111: 153–169
SteinertPM (1990) J. Biol. Chem. 265: 8766–8774
FuchsE & GreenH (1980) Cell 19: 1033–1042
AebiU, FowlerWE, RewP, & SunTT (1983) J. Cell Biol. 97: 1131–1143
HohlD, MehrelT, LichtiU, TurnerML, RoopDR, & SteinertPM (1991) J. Biol. Chem. 266: 6626–6636
MehrelT, HohlD, RothnagelJA, LongleyMA, BundmanD, ChengC, LichtiU, BisherME, StevenAC, SteinertPM, YuspaSH, & RoopDR (1990) Cell 61: 1103–1112
OshimaRG, TrevorK, ShevinskyLH, RyderOA, & CecenaG (1988) Genes Dev. 2: 505–516
OshimaRG, AbramsL, & KuleshD (1990) Genes Dev. 4: 835–848
MullerR & WagnerEF (1984) Nature 311: 438–442
TakemotoY, FujimuraY, MatsumotoM, TamaiY, MoritaT, MatsushiroA, & NozakiM (1991) Nucleic Acids Res. 19: 2761–2765
TamaiY, TakemotoY, MatsumotoM, MoritaT, MatsushiroA, & NozakiM (1991) Gene 104: 169–176
ByrneC & FuchsE (1993) Mol. Cell Biol. 13: 3176–3190
MagnaldoT, VidalRG, OhtsukiM, FreedbergIM, & BlumenbergM (1993) Gene Expr. 3: 307–315
OhtsukiM, Tomic-CanicM, FreedbergIM, & BlumenbergM (1992) J. Invest. Dermatol. 99: 206–215
OhtsukiM, FlanaganS, FreedbergIM, & BlumenbergM (1993) Gene Expr. 3: 201–213
CasatorresJ, NavarroJM, BlessingM, & JorcanoJL (1994) J. Biol. Chem. 269: 20489–20496
LeaskA, ByrneC, & FuchsE (1991) Proc. Natl. Acad. Sci. U.S.A. 88: 7948–7952
LeaskA, RosenbergM, VassarR, & FuchsE (1990) Genes Dev. 4: 1985–1998
HuffCA, YuspaSH, & RosenthalD (1993) J. Biol. Chem. 268: 377–384
LuB, RothnagelJA, LongleyMA, TsaiSY, & RoopDR (1994) J. Biol. Chem. 269: 7443–7449
RothnagelJA, GreenhalghDA, GagneTA, LongleyMA, & RoopDR (1993) J. Invest. Dermatol. 101: 506–513
YuspaSH, KilkennyAE, SteinertPM, & RoopDR (1989) Cell Biol. 109: 1207–1217
DlugoszAA & YuspaSH (1993) J. Cell Biol. 120: 217–225
HohlD, LichtiU, BreitkreutzD, SteinertPM, & RoopDR (1991) J. Invest. Dermatol. 96: 414–418
YonedaK & SteinertPM (1993) Proc. Natl. Acad. Sci. U.S.A. 90: 10754–10758
DisepioD, JonesA, LongleyMA, BundmanD, RothnagelJA, & RoopDR (1995) J. Biol. Chem. 270: 10792–10799
RiceRH & GreenH (1979) Cell 18: 681–694
EckertRL, YaffeMB, CrishJF, MurthyS, RorkeEA, & WelterJF (1993) J. Invest. Dermatol. 100: 613–617
YaffeMB & EckertRL (1993) J. Invest. Dermatol. 100: 3–9
WelterJF & EckertRL (1995) Oncogene 11: 2681–2687.
YounusJ & GilchrestBA (1992) J. Cell. Physiol. 152: 232–239
ClinePR & RiceRH (1983) Cancer Res. 43: 3203–3207
SuMJ, BikleDD, ManciantiML, & PillaiS (1994) J. Biol. Chem. 269: 14723–14729
CarrollJM, AlbersKM, GarlickJA, HarringtonR, & TaichmanLB (1993) Proc. Natl. Acad. Sci. U.S.A. 90: 10270–10274
CrishJF, HowardJM, ZaimTM, MurthyS, & EckertRL (1993) Differentiation 53: 191–200
TakahashiH & IizukaH (1993) J. Invest. Dermatol. 100: 10–15
WelterJF, CrishJF, AgarwalC, & EckertRL (1995) J. Biol. Chem. 270: 12614–12622
EckertRL & GreenH (1986) Cell 46: 583–589
CarrollJM & TaichmanLB (1992) J. Cell Sci. 103: 925–930
LiewFM & YamanishiK (1992) Exp Cell Res. 202: 310–315
YamadaK, YamanishiK, KakizukaA, KibeY, DoiH, & YasunoH (1994) Biochem. Mol. Biol. Int. 34: 827–836
ThierryF, SpyrouG, YanivM, & HowleyP (1992) J. Virol. 66: 3740–3748
StabelS & ParkerPJ (1991). Pharmacol. Ther., 51: 71–95
NishizukaY (1992) Science 258: 607–614
RheeSG & ChoiKD (1992) J Biol. Chem. 267: 12393–12396
BlumbergPM (1988) Cancer Res. 48: 1–8
JalavaA, LintunenM, & HeikkilaJ (1993) Biochem. Biophys. Res. Commun. 191: 472–478
SzallasiZ, DenningMF, SmithCB, DlugoszAA, YuspaSH, PettitGR, & BlumbergPM (1994) Mol. Pharmacol 46: 840–850
DenningMF, DlugoszAA, HowettMK, & YuspaSH (1993) J. Biol. Chem. 268: 26079–26081
CazaubonSM & ParkerPJ (1993) J. Biol. Chem. 268: 17599–17563
SandoJJ, MaurerMC, BolenEJ, & GrishamCM (1992) Cell Signal. 4: 595–609
BellRM & BurnsDJ (1991) J Biol. Chem. 266: 4661–4664
NilesRM (1994) Adv. Exp. Med. Biol. 354: 37–57
MailhosC, HowardMK, & LatchmanDS (1994) Brain Res. 644: 7–12
OtteAP & MoonRT (1992) Cell 68: 1021–1029
MischakH, PierceJH, GoodnightJ, KazanietzMG, BlumbergPM, & MushinskiJF (1993) J. Biol. Chem. 268: 20110–20115
MischakH, GoodnightJA, KolchW, Martiny-BaronG, SchaechtleC, KazanietzMG, BlumbergPM, PierceJH, & MushinskiJF (1993) J Biol. Chem. 268: 6090–6096
DlugoszAA (1995) In: MukhtarH (Ed) Skin Cancer: Mechanisms & Human Relevance (pp. 199–206) CRC Press, Ann Arbor
OsadaS, MizunoK, SaidoTC, AkitaY, SuzukiK, KurokiT, & OhnoS (1990) J. Biol. Chem. 265: 22434–22440
OsadaS, HashimotoY, NomuraS, KohnoY, ChidaK, TajimaO, KuboK, AdimotoK, KoizumiH, KitamuraY, SuzukiK, OhnoS, & KurokiT (1993) Cell Growth Diff. 4: 167–175
DlugoszAA, MischakH, MushinskiJF, & YuspaSH (1992) Mol. Carcinog. 5: 286–292
IsseroffRR, StephensLE, & GrossJL (1989) J. Cell Physiol. 141: 235–242
DunnJA, JengAY, YuspaSH, & BlumbergPM (1985) Cancer Res. 45: 5540–5546
MatsuiMS, ChewSL, & DeLeoVA (1992) J Invest Dermatol. 99: 565–571
DlugoszAA, ChengC, WilliamsEK, DhariaAG, DenningMF, & YuspaSH (1994) Cancer Res., 54: 6413–6420
LeeE & YuspaSH (1991) Carcinogenesis 12: 1651–1658
DlugoszAA & YuspaSH (1993) J Cell Biol. 120: 217–225
DlugoszAA & YuspaSH (1994) J. Invest. Dermatol. 102: 409–414
SzallasiZ, DenningMF, SmithCB, DlugoszAA, YuspaSH, PettitGR, & BlumbergPM (1994) Mol. Pharmacol. 46: 840–850
PunnonenK, DenningMF, LeeE, LiL, RheeSG, & YuspaSH (1993) J. Invest. Dermatol. 101: 719–726
TangW, ZibohVA, IsseroffRR, & MartinezD (1988) J Invest Dermatol. 90: 37–43
JakenS & YuspaSH (1988) Carcinogenesis, 9: 1033–1038
KruszewskiFH, HenningsH, YuspaSH, & TuckerRW (1991) Am. J. Physiol. 261: C767–773
ZibohVA, IsseroffRR, & PandeyR (1984) Biochem. Biophys. Res. Comun. 122: 1234–1240
ReynoldsNJ, BaldassareJJ, HendersonPA, ShulerJL, BallasLM, BurnsDJ, MoomawCR & FisherGJ (1994) J. Invest. Dermatol. 103: 364–369
HegemannL, BonnekohB, vanRooijenLA, & MahrleG (1992) J. Dermatol. Sci., 4: 18–25
JonesKT & SharpeGR (1994) J. Cell Physiol. 159: 324–330
MatsuiMS, IllardaI, WangN, & DeLeoVA (1993) Exp. Dermatol. 2: 247–256
HegemannL, KempenaarJ, & PonecM (1994) Arch. Dermatol. Res. 286: 278–284
MatsuiMS, WangN, MacFarlaneD, & DeLeoVA (1994) Photochem. Photobiol. 59: 53–57
GherziR, SparatoreB, PatroneM, SciuttoA, & BriataP (1992) Biochem. Biophys. Res. Commun. 184: 283–291
JonesKT & SharpeGR (1994) Exp. Cell Res. 210: 71–76
RansoneLJ & VermaIM (1990) Annu. Rev. Cell Biol. 6: 539–557
CohenDR & CurranT (1989) Crit. Rev. Oncog. 1: 65–88
CohenDR, FerreiraPC, GentzR, FranzaBRJr., & CurranT (1989) Genes Dev. 3: 173–184
NishinaH, SatoH, SuzukiT, SatoM, & IbaH (1990) Proc. Natl. Acad. Sci. U.S.A. 87: 3619–3623
SuzukiT, OkunoH, YoshidaT, EndoT, NishinaH, & IbaH (1991) Nucl. Acids Res. 19: 5537–5542
RyderK & NathansD (1988) Proc. Natl. Acad. Sci. U.S.A. 85: 8464–8467
RyderK, LanahanA, Perez-AlbuerneE, & NathansD (1989) Proc. Natl. Acad. Sci. U. S. A. 86: 1500–1503
HiraiSI, RyseckRP, MechtaF, BravoR, & YanivM (1989) EMBO J. 8: 1433–1439
LeeW, HaslingerA, KarinM, & TijianR (1987) Nature 325, 368–372
WoodgettJR, PulvererBJ, NilolakakiE, PlyteS, HughesK, FranklinCC, & KraftAS (1993) In: BrownBL & DobsonPRM (eds) Advances in second messenger & phosphoprotein research, Vol. 28 (pp. 261–269) Raven Press, New York
KovaryK & BravoR (1992) Mol. Cell. Biol. 12: 5015–5023
BoiseLH, PetryniakB, MaoX, JuneCH, WangCY, LindstenT, BravoR, KovaryK, LeidenJM, & ThompsonCB (1993) Mol. Cell. Biol. 13: 1911–1919
RednerRL, LeeAW, OsawaGA, & NienhuisAW (1992) Oncogene 7: 43–50
CandeliereGA, Prud'hommeJ, & St-ArnaudR (1991) Mol. Endocrinol. 5: 1780–1788
CurranT (1988) In: ReddyEP, SkalkaAM, & CurranT (Eds) The Oncogene Handbook (pp. 307–325) Elsevier, Amsterdam.
Basset-SeguinN, EscotC, BlanchardJM, KeraiC, VerrierB, MionH, & GuilhouJJ (1990) J. Invest. Dermatol. 94: 418–422
SmeyneRJ, VendrellM, HarywardM, BakerSJ, MiaoGG, SchillingK, RobertsonLM, CurranT, & MorganJI (1993) Nature 363: 166–169
BriataP, d'AnnaF, FranziAT, & GherziR (1993) Exp. Cell Res. 204: 136–146
FisherC, ByersMR, IadarolaMJ, & PowersEA (1991) Development 111: 253–258
GandarillasA, & WattFM (1995) Oncogene 11: 1403–1407
SmeyneRJ, SchillingK, RobertsonL, LukD, OberdickJ, CurranT, & MorganJI (1992) Neuron 8: 13–23
BernerdF, MagnaldoT, FreedbergIM, & BlumenbergM (1993) Gene Expr. 3: 187–199
Basset-SeguinN, EscotC, MolesJP, BlanchardJM, KeraiC, & GuilhouJJ (1991) J. Invest. Dermatol. 97: 672–678
CeruttiP, ShahG, PeskinA, & AmstakP (1992) Ann. N. Y. Acad. Sci. 663: 158–166
ElderJT, TavakkolA, KleinSB, ZeiglerME, WichaMW, & VoorheesJJ (1990) J. Invest. Dermatol. 94: 19–25
GillardonF, EschenfelderC, UhlmannE, HartschuhW, & ZimmermannM (1994) Oncogene 9: 3219–3225
LuYP, ChangRL, LouYR, HuangMT, NewmarkHL, ReuhlKR, & ConneyAH (1994) Carcinogenesis 15: 2363–2370
ShahG, GhoshR, AmstadPA, & CeruttiPA (1993) Cancer Res. 53: 38–45
JohnsonRS, SpiegelmanBM, & PapaioannouV (1992) Cell 71: 577–586
DottoGP, GilmanMZ, MaruyamaM, & WeinbergRA (1986) EMBO J., 5: 2853–2857
DiFiorePP, FalcoJ, BorrelloI, WeissmanB, & AaronsonSA (1988) Mol. Cell Biol. 8: 557–563
ReissM, RadinAI, & WeisbergTF (1990) Cancer Res. 50: 6641–6648
RysekRP & BravoR (1991) Oncogene. 6: 533–542
BernsteinLR, FerrisDK, ColburnNH, & SobelME (1994) J. Biol. Chem. 269: 9401–9404
AuwerxJ, Sassone-CorsiP (1992) Oncogene 7: 2271–2280
AngelP, ImagawaM, ChiuR, SteinB, ImbraRJ, RahmsdorfHJ, JonatC, HerrlichP, & KarinM (1987) Cell. 49: 729–739
BarberJR, Sassone-CorsiP, & VermaIM (1987) Ann. N.Y. Acad. Sci. 511: 117–130
GilleH, SharrocksAD, & ShawPE (1992) Nature 358: 414–417
MaraisR, WynneJ, & TreismanR (1993) Cell 73: 381–393
HibiM, LinA, SmealT, MindenA, & KarinM (1993) Genes Dev. 7: 2135–2148
SuB, JacintoE, HibiM, KallunkiT, KarinM, & Ben-Neriah (1994) Cell 77: 727–736
BernsteinLR, FerrisDK, ColburnNH, & SobelME (1994) J. Biol. Chem. 269: 9401–9404
PulvererBJ, KyriakisJM, AvruchJ, NikolakakiE, & WoodgettJR (1991) Nature 353: 670–674
BinetruyB, SmealT, & KarinM (1991) Nature 351: 122–127
KharbandaS, SaleemA, EmotoY, StoneR, RappU, & KufeD (1994) J. Biol. Chem. 269: 872–878
BoyleWJ, SmealT, DefizeLH, AngelP, WoodgettJR, KarinM, & HunterT (1991) Cell 64: 573–584
FranklinCC, SanchezV, WagnerF, WoodgettJR, & KraftAS (1992) Proc. Natl. Acad. Sci. USA 89: 7247–7251
LeeWY, ButlerAP, LocniskarMF, & FischerSM (1994) J. Biol. Chem. 269: 17971–17980
KerppolaTK, LukD, & CurranT (1993) Mol. Cell Biol. 13: 3782–3791
MinerJN, DiamondMI, YamamotoKR (1991) Cell Growth Diff. 2: 525–530
KonigH, PontaH, RahmsdorfHJ, & HerrlichP (1992) EMBO J. 11: 2241–2246
RobertsonLM, KerppolaTK, VendrellM, LukD, SmeyneRJ, BocchiaroC, MorganJI, & CurranT (1995) Neuron 14: 241–252
CastellazziM, SpyrouG, LaVistaN, DangyJP, PiuF, YanivM, & BrunG (1991) Proc. Natl. Acad. Sci. U.S.A. 88: 8890–8894
SuzukiT, OkunoH, YoshidaT, EndoT, NishinaH, & IbaH (1991) Nucleic Acids Res. 19: 5537–5542
Gizang-GinsbergE & ZiffEB (1994) Mol. Endocrinol. 8: 249–262
WilliamsT & TjianR (1991) Genes Dev. 5: 670–682
KachinskasDJ, PhillipsMA, QinQ, StokesJD, & RiceRH (1994) Cell Growth Diff. 5: 1235–1241
ByrneC, TainskyM, & FuchsE (1994) Development 120: 2369–2383
WegnerM, DroletDW, & RosenfeldMG (1993) Curr. Opin. Cell. Biol. 5: 488–498
AndersenB, SchonemannMD, FlynnSE, PearseRV, SinghH, & RosenfeldM.G., (1993) Science 260: 78–82
FausI, HsuHJ, & FuchsE (1994) Mol. Cell. Biol. 14: 3263–3275
WelterJF, GaliH, CrishJ, & EckertRL (1996) J. Biol. Chem. 271: 14727–14733
BotasJ (1993) Curr. Opin. Cell Biol. 5: 1015–1022
KomuvesLG, ShenWF, RozenfeldSM, EliasPM, & LargmanC (1995) J. Invest. Dermatol. 104: 559
DarnellJE, KerrIM, & StarkGR (1994) Science 264: 1415–1421
JiangCK, FlanaganS, OhtsukiM, ShuaiK, FreedbergIM, & BlumenbergM (1994) Mol. Cell. Biol. 14: 4759–4769
TsengH & GreenH (1992) Proc. Natl. Acad. Sci. U.S.A. 89: 10311–10315
TsengH & GreenH (1994) J. Cell. Biol. 126: 495–506
CripeTP, AlderbornA, AndersonS, ParkkinenS, BergmanP, HaugenU., PetterssonU, & TurekLP (1990) New Biol. 2: 450–463
MackDH & LaiminsLA (1991) Proc.Natl. Acad. Sci. U.S.A. 88: 9102–9106
OffordEA & BeardP (1990) J. Virol. 64: 4792–4798
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Eckert, R.L., Welter, J.F. Transcription factor regulation of epidermal keratinocyte gene expression. Molecular Biology Reports 23, 59–70 (1996). https://doi.org/10.1007/BF00357073
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DOI: https://doi.org/10.1007/BF00357073