Tài liệu Báo cáo khoa học: Roles of AP-2 transcription factors in the regulation of cartilage and

REVIEW ARTICLE

Roles of AP-2 transcription factors in the regulation of

cartilage and skeletal development

Ann-Kathrin Wenke and Anja K. Bosserhoff

Institute of Pathology, University of Regensburg, Germany

The AP-2 family

AP-2a was first identified by its ability to bind to enhan￾cer regions of SV40 and human metallothionein IIA [1].

The AP-2 family of transcription factors is composed of

five members: AP-2a, AP-2b, AP-2c, AP-2d, and AP-2e

[2–7], described for humans and mice. Orthologs of

some AP-2s have also been found in frogs and fish, and

homologs occur in invertebrates. All AP-2s have a

highly conserved basic helix–span–helix DNA-binding

and dimerization domain at their C-terminus, and a less

conserved proline-rich and glutamine-rich transactiva￾tion domain at their N-terminus [8–10]. Most isoforms

also have a PY-motif (XPPXY) in the N-terminal trans￾activation domain that is important for their role as

transcriptional activators [9]. The AP-2 factors form

homodimers and heterodimers for their transcriptional

activity. A multiple alignment of all five human AP-2s,

illustrating their domain structure, is shown in Fig. 1.

A detailed and extensive overview of the AP-2 family

is given in the review of Eckert et al., [11] which also

contains a schematic illustration of the AP-2 structure.

Expression patterns of AP-2 molecules

and functional implications

The expression and function of AP-2 isoforms have

been systematically analyzed during murine embryo￾genesis and in studies of the corresponding knockout

mice.

AP-2a, AP-2b and AP-2c show partially overlap￾ping expression patterns in neural crest cells (NCCs),

the peripheral nervous system, the facial mesenchyme,

the limbs, various epithelia of the developing embryo,

Keywords

AP-2; cartilage; chondrogenesis; limb;

transcriptional regulation

Correspondence

A.-K. Bosserhoff, Institute of Pathology,

University of Regensburg,

Franz-Josef-Strauss-Allee 11, D-93053

Regensburg, Germany

Fax: +49 941 944 6602

Tel: +49 941 944 6705

E-mail: [email protected]

burg.de

(Received 12 October 2009, revised 13

November 2009, accepted 20 November

2009)

doi:10.1111/j.1742-4658.2009.07509.x

During embryogenesis, most of the mammalian skeletal system is preformed

as cartilaginous structures that ossify later. The different stages of cartilage

and skeletal development are well described, and several molecular factors

are known to influence the events of this enchondral ossification, especially

transcription factors. Members of the AP-2 family of transcription factors

play important roles in several cellular processes, such as apoptosis, migra￾tion and differentiation. Studies with knockout mice demonstrate that a main

function of AP-2s is the suppression of terminal differentiation during

embryonic development. Additionally, the specific role of these molecules as

regulators during chondrogenesis has been characterized. This review gives

an overview of AP-2s, and discusses the recent findings on the AP-2 family,

in particular AP-2a, AP-2b, and AP-2e, as regulators of cartilage and skeletal

development.

Abbreviations

NCC, neural crest cell; RA, retinoic acid; ZPA, zone of polarizing activity.

894 FEBS Journal 277 (2010) 894–902 ª 2009 The Authors Journal compilation ª 2009 FEBS