Fos and jun: The AP-1 connection

Curran, Tom; Franza, B. R.

doi:10.1016/0092-8674(88)90024-4

Cited by 1,554 publications

(712 citation statements)

References 0 publications

Supporting

Mentioning

688

Contrasting

Unclassified

Order By: Relevance

“…V-fos encodes the transforming agent of the FBR murine sarcoma virus, and forms part of the transcription factor AP-1 (Finkel et al, 1975;van Beveren et al, 1984;Curran and Verma, 1984;Curran and Franza, 1988). AP-1 is a heterodimeric protein composed of various combinations of the Jun and Fos family proteins, and this¯exibility permits transactivation or transrepression of gene expression (Bushel et al, 1995;De Cesare et al, 1995;reviewed in Karin et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Krp1, a novel kelch related protein that is involved in pseudopod elongation in transformed cells

et al. 2000

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Krp1, a novel kelch related protein that is involved in pseudopod elongation in transformed cells

et al. 2000

View full text Add to dashboard Cite

“…Since the AP-1 transcription factor complex is a well-de®ned nuclear target of PKC activation (reviewed in Hill and Treisman, 1995), our current studies are focused upon understanding the role of AP-1 in the regulation of events related to keratinocyte di erentiation. The AP-1 transcription factor complex is composed of heterodimers formed between members of the Jun and Fos families that bind to DNA in a sequence-speci®c manner (reviewed in Curran and Franza, 1988;Angel and Karin, 1991). The Jun family consists of three proteins (c-Jun, Jun B and Jun D) while the Fos family is composed of four proteins (c-Fos, Fos B, Fra-1 and Fra-2) that require heterodimerization with Jun proteins or other members of the bZIP superfamily of DNA binding proteins (Johnson and McKnight, 1989) to bind to DNA.…”

Section: Introductionmentioning

confidence: 99%

Opposing activities of c-Fos and Fra-2 on AP-1 regulated transcriptional activity in mouse keratinocytes induced to differentiate by calcium and phorbol esters

Rutberg

Sáez

et al. 1997

Oncogene

View full text Add to dashboard Cite

The major di erentiation products of maturing keratinocytes contain AP-1 regulatory motifs, and AP-1 DNA binding activity increases in cultured keratinocytes induced to di erentiate by calcium. Here, we have analysed AP-1 transcriptional activity in mouse keratinocytes treated with calcium and 12-O-tetradecanoyl phorbol-13-acetate (TPA), two agents that induce terminal di erentiation of keratinocytes with di erent phenotypic consequences. Reporter constructs representing multimers of AP-1 sequences found in keratinocyte marker genes demonstrated that the calcium-induced AP-1 DNA binding activity does not correlate with transcriptional activation. Moreover, expression from active subunits of the pro®laggrin and spr 1 promoters increased in calcium-treated keratinocytes when the AP-1 sites were disrupted, indicating that AP-1 may negatively regulate certain promoters in these cells. In contrast, AP-1 reporter activity was increased in keratinocytes treated with TPA. This induction was dependent upon the expression of c-Fos since AP-1 transcriptional activity was not increased in TPA-treated keratinocytes derived from c-fos null mice. Analysis of AP-1 protein expression in calcium-and TPA-treated keratinocytes demonstrated that only TPA increased the expression of c-Jun, while Jun B and Jun D were induced by both of these agents. c-Fos was expressed only in TPA treated keratinocytes, Fra-2 was expressed only in calcium-treated cells, and Fra-1 was expressed in both. Exogenous expression of Fra-2 repressed AP-1 transcriptional activity in TPA-treated keratinocytes, while c-Fos expression activated the AP-1 sequence in calcium-treated keratinocytes. These data indicate that Fra-2 and c-Fos play opposing roles in regulating AP-1 activity in keratinocytes and that multiple inducerdependent regulatory pathways may exist for the expression of keratinocyte di erentiation markers.

show abstract

“…Apart from its identification as a DNA repair protein, HAPI has been shown to regulate the reductive activation of oxidized transcription factors, such as AP-1, Myb, Rel and NF-kB (Curran et al, 1988;Abate et al, 1990;Frame et al, 1991;. This reduction-oxidation (redox) activity is dependent on a cysteine residue located near the DNA binding domain of the factor and is structurally and functionally distinct from the repair activity of HAPI (Walker et al, 1993;.…”

mentioning

confidence: 99%

Human AP endonuclease 1 (HAP1) protein expression in breast cancer correlates with lymph node status and angiogenesis

Kakolyris

Kaklamanis²,

Engels³

et al. 1998

Br J Cancer

View full text Add to dashboard Cite

Summary Human AP endonuclease (HAP1) plays a major role in the repair of apurinic/apyrimidinic (AP) sites in cellular DNA. We used immunohistochemistry to examine the expression of HAP1 in normal breast and in 102 primary breast carcinomas. In normal breast epithelium, HAP1 had a uniformly nuclear localization. However, in lactating glandular epithelium, the expression of HAP1 was predominantly cytoplasmic. In carcinomas, both nuclear and cytoplasmic (44%), cytoplasmic (28%) or nuclear staining (24%) were observed. In four cases (4%), no HAP1 expression was detected. All patterns of expression for HAP1 were demonstrated for ductal carcinomas in situ (DCIS), although comedo-type DCIS were usually accompanied by mostly cytoplasmic staining. Similarly, the HAP1 expression in regions of invasive tumour necrosis was cytoplasmic. Pure nuclear HAP1 expression was significantly correlated with low angiogenesis (P = 0.007) and negative lymph node status (P = 0.001). In contrast, cases with cytoplasmic as well as nuclear staining were associated with poor prognostic factors, such as high angiogenesis (P = 0.03) and node positivity (P = 0.03). The pure nuclear staining may be related to better differentiation, as in normal breast, and hence better prognostic features, and cytoplasmic staining to a more metabolically active phenotype with high protein synthesis, as in lactating breast.Keywords: HAP1; breast cancer; immunohistochemistry; DNA repairThe DNA of all organisms, although inherently stable, is under constant threat from both endogenous and exogenous factors. The DNA repair process is of fundamental importance for the survival of all species, and recent studies have established the association of defective DNA repair machinery and cancer (Fishel et al, 1993;Leach et al, 1993).One of the most common lesions that arise in cellular DNA is the apurinic/apyrimidinic (AP) site, which results from the hydrolysis of the N-glycosyl bond linking the base to the deoxyribose moiety. AP sites are considered to be both cytotoxic and mutagenic, and they have been estimated to occur spontaneously at a rate of approximately 104 cell-' day-' from the mammalian cell genome (Loeb et al, 1986). Reactive oxygen species generated either during normal cellular metabolism or by exogenous agents, such as ionizing radiation, can increase this high error rate still further (Hutchinson, 1985;Teoule, 1987).There are specific DNA repair enzymes that recognize AP sites. The major human AP endonuclease (HAPI), also known as APE, APEX or Ref-1, is a 37-kDa protein that shows strong primary sequence similarity to Escherichia coli exonuclease III protein (Demple et al, 1991;Seki et al, 1991; Correspondence to: AL Harris residue is subsequently removed by a phosphodiesterase, followed by filling in of the nucleotide gap by DNA polymerase and DNA ligase, which seals the nick and permits the accurate progress of a DNA replication fork.Apart from its identification as a DNA repair protein, HAPI has been shown to regulate the reductive activation of oxidiz...

show abstract

Fos and jun: The AP-1 connection

Cited by 1,554 publications

References 0 publications

Krp1, a novel kelch related protein that is involved in pseudopod elongation in transformed cells

Krp1, a novel kelch related protein that is involved in pseudopod elongation in transformed cells

Opposing activities of c-Fos and Fra-2 on AP-1 regulated transcriptional activity in mouse keratinocytes induced to differentiate by calcium and phorbol esters

Human AP endonuclease 1 (HAP1) protein expression in breast cancer correlates with lymph node status and angiogenesis

Contact Info

Product

Resources

About