Deciphering AP-1 function in tumorigenesis: fra-ternizing on target promoters.
Multi-gene families of transcription factors pose a formidable challenge to molecular and functional analysis. Dissecting distinct functions for individual family members requires a combination of approaches in different cellular and animal models. The AP-1 transcription factor complex serves as a paradigm for understanding the dynamics of transcriptional regulation. Knockout, knockdown and transgenic strategies, inducible alleles, mutational analysis, chemical genetics, etc.; researchers have applied all the tricks of the trade to understand how AP-1 works. AP-1 refers to a mixture of dimers formed between members of the Jun, Fos and ATF families. The complexity of the AP-1 biological functions reflects the wide combinatorial diversity of its components. AP-1 has been linked to cancer and neoplastic transformation ever since the first jun and fos genes were cloned as cellular homologues of viral oncogenes twenty years ago. Because of the oncogenic or tumor suppressive activity exhibited by distinct Jun and Fos nuclear proteins depending on the cell context and the genetic background of the tumor, the AP-1 complex has been called a "double-edged sword" in tumorigenesis. The cumulating results over the last decade are finally leading to the identification of specific functions for individual AP-1 components and their contribution to neoplastic disease. Here, we focus on the Fra-1 protein in tumorigenesis, which offers an illustrative example of this helter-skelter voyage.
Verde
Pasquale
P
Institute of Genetics and Biophysics A. Buzzati Traverso, CNR, Naples, Italy. verde@igb.cnr.it
Casalino
Laura
L
Talotta
Francesco
F
Yaniv
Moshe
M
Weitzman
Jonathan B
JB
D000818:Animals; D018390:Gene Targeting / Q000379:methods; D006801:Humans; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009369:Neoplasms / Q000737:chemistry / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D000099169:Fos-Related Antigen 1
D009363:Neoplasm Proteins; D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; D000099169:Fos-Related Antigen 1