Suppression of AP1 Transcription Factor Function in Keratinocyte Suppresses Differentiation

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Jun 1

PMID 22649503

Citations 18

Authors

Bingshe Han

Ellen A Rorke

Gautam Adhikary

Yap Ching Chew

Wen Xu

Richard L Eckert

Affiliations

Soon will be listed here.

Abstract

Our previous study shows that inhibiting activator protein one (AP1) transcription factor function in murine epidermis, using dominant-negative c-jun (TAM67), increases cell proliferation and delays differentiation. To understand the mechanism of action, we compare TAM67 impact in mouse epidermis and in cultured normal human keratinocytes. We show that TAM67 localizes in the nucleus where it forms TAM67 homodimers that competitively interact with AP1 transcription factor DNA binding sites to reduce endogenous jun and fos factor binding. Involucrin is a marker of keratinocyte differentiation that is expressed in the suprabasal epidermis and this expression requires AP1 factor interaction at the AP1-5 site in the promoter. TAM67 interacts competitively at this site to reduce involucrin expression. TAM67 also reduces endogenous c-jun, junB and junD mRNA and protein level. Studies with c-jun promoter suggest that this is due to reduced transcription of the c-jun gene. We propose that TAM67 suppresses keratinocyte differentiation by interfering with endogenous AP1 factor binding to regulator elements in differentiation-associated target genes, and by reducing endogenous c-jun factor expression.

Citing Articles

Retraction: Suppression of AP1 Transcription Factor Function in Keratinocyte Suppresses Differentiation.

PLoS One. 2021; 16(2):e0247222.

PMID: 33571274 PMC: 7877661. DOI: 10.1371/journal.pone.0247222.

Kdm6b regulates context-dependent hematopoietic stem cell self-renewal and leukemogenesis.

Mallaney C, Ostrander E, Celik H, Kramer A, Martens A, Kothari A Leukemia. 2019; 33(10):2506-2521.

PMID: 30936419 PMC: 6773521. DOI: 10.1038/s41375-019-0462-4.

Expression profiling and bioinformatic analyses suggest new target genes and pathways for human hair follicle related microRNAs.

Hochfeld L, Anhalt T, Reinbold C, Herrera-Rivero M, Fricker N, Nothen M BMC Dermatol. 2017; 17(1):3.

PMID: 28228108 PMC: 5322611. DOI: 10.1186/s12895-017-0054-9.

Interleukin-4 Downregulation of Involucrin Expression in Human Epidermal Keratinocytes Involves Stat6 Sequestration of the Coactivator CREB-Binding Protein.

Bao L, Alexander J, Zhang H, Shen K, Chan L J Interferon Cytokine Res. 2016; 36(6):374-81.

PMID: 26918372 PMC: 4892208. DOI: 10.1089/jir.2015.0056.

MEP50/PRMT5 Reduces Gene Expression by Histone Arginine Methylation and this Is Reversed by PKCδ/p38δ Signaling.

Saha K, Adhikary G, Eckert R J Invest Dermatol. 2016; 136(1):214-224.

PMID: 26763441 PMC: 4899982. DOI: 10.1038/JID.2015.400.

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