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The activating protein-1 transcriptional complex

Essential and multifaceted roles in bone

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Clinical Reviews in Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

The activating protein-1 (AP-1) family of transcriptional mediators is composed of dimers of Jun and Fos family members that have other potential partners such as the activating transcription factor (ATF) and musculoaponeurotic fibrosarcoma (Maf) protein families as well. AP-1 is one of the first and most well-characterized transcriptional mediators known with noted impact described in the literature for most tissues in the body. The skeletal impact of AP-1 has been intensively investigated, and extensive information exists for the role of various AP-1 proteins in osteoblast and chondrocyte activities in vitro. Numerous genes important in skeletal biology such as the receptor activator of nuclear factor (NF)-ϰB-ligand (RANKL), osteocalcin (OCN), runx2, collagens, and bone morphogenetic proteins (BMPs) contain AP-1 sites in their promoters, and key hormonal controls of skeletogenesis rely on AP-1 for their activities. Gene-targeted murine models with loss and gain of function for the various AP-1 family members have been particularly informational in the understanding of AP-1 in bone. The complex signaling network that is emerging for osteoclast differentiation reveals a critical role for AP-1. The context of the AP-1, the composition of the dimerizations and the temporal presentation of the downstream activities of AP-1 are integral to the balance of osteoblast and osteoclast function.

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Abbreviations

ALP:

alkaline phosphatase

AP-1:

activating protein-1

ATF:

activating transcription factor

BMP:

bone morphogenetic protein

BSP:

bone sialoprotein

bZIP:

basic-leucine zipper

CDK:

cyclin-dependent kinase

COL 1a2:

collagen type I α 2

CRE:

cAMP responsive element

CREB:

CRE binding

DMP:

dentin matrix protein

EREs:

estrogen-responsive DNA elements

ERs:

estrogen receptors

GM-CSF:

granulocyte macrophage-colony stimulating factor

IEG:

immediate early gene

IFN:

interferon

IGFs:

insulin-like growth factors

IKK:

inhibitor of NF-ϰB (I-ϰB) kinase

IL-1:

interleukin-1

JNK:

Jun N-terminal kinase

MAF:

musculoaponeurotic fibrosarcoma

MAP:

mitogen-activated protein

MGP:

matrix Gla protein

MITF:

microphthalmia transcription factor

MKK7:

MAP kinase kinase 7

MMP:

matrix metalloproteinases

NFAT:

nuclear factor of activated T-cell

OCN:

osteocalcin

OPG:

osteoprotegerin

OPN:

osteopontin

P38MAPK:

p38 MAP kinase

PKA:

protein kinase A

PKC:

protein kinase C

PTH:

parathyroid hormone

PTHrP:

parathyroid hormone-related protein

RANKL:

receptor activator of NF-ϰB-ligand

RSK:

ribosomal S6 kinase

SRE:

serum response element

SRF:

serum response factor

TGF:

transforming growth factor

TIMPs:

tissue inhibitors of MMP

TPA:

12-O-tetradecanoylphorbol-13 acetate

TRAF:

TNF-receptor associated factor

TRAP:

tartrate-resistant acid phosphatase

TRE:

TPA responsive element

VEGF:

vascular endothelial growth factor

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Authors and Affiliations

  1. Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, 1011 North University Avenue, 48109-1078, Ann Arbor, MI

    Junro Yamashita DDS, PhD & Laurie K. McCauley DDS, PhD

  2. Department of Biologic and Materials Science, School of Dentistry, University of Michigan, Ann Arbor, MI

    Junro Yamashita DDS, PhD

  3. Department of Pathology, Medical School, University of Michigan, Ann Arbor, MI

    Laurie K. McCauley DDS, PhD

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  1. Junro Yamashita DDS, PhD
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Correspondence to Laurie K. McCauley DDS, PhD.

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Yamashita, J., McCauley, L.K. The activating protein-1 transcriptional complex. Clinic Rev Bone Miner Metab 4, 107–122 (2006). https://doi.org/10.1385/BMM:4:2:107

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