CJun A Component of AP1

The Jun protein was originally identified in transformed cells carrying the genome of a replication defective avian sarcoma virus 17 (ASV 17) that directs the expression of a 65-kDa gag-jun fusion product, designated as v-Jun (Maki et al., 1987; Bos et al., 1988). Soon after, its homolog, the proto-oncogene c-Jun, was isolated from human and murine tissues (Bohmann et al., 1987; Ryder et al., 1988). c-Jun shares sequence similarity not only with v-jun, but also with the yeast transcription regulatory protein GCN4. GCN4 binds to a DNA element that is bound also by the mammalian AP-1, known at that time only as a transcription factor interacting with specific enhancer sequences (Haluska et al., 1988; Short, 1987). The co-purification of c-Jun as the Fos-binding protein p39 from an AP-1 oligonucleotide affinity chromatography was the first indication that AP-1 was a heterodimeric transcription factor complex of c-Jun and Fos (Rauscher, III et al., 1988b; Rauscher, III et al., 1988a; Angel et al., 1988a; Harshman et al., 1988).

c-Jun and Fos are both basic-leucine zipper proteins. Unlike c-Jun, which can bind to AP-1 DNA site as a homodimer, Fos and other Fos family proteins only heterodimerize with Jun. Dimerization is determined by the "leucine zipper" domain; exchanging the leucine zipper in Fos with that of c-Jun generates a protein that forms a complex with Fos (Neuberg et al., 1989; O'Shea et al., 1989; Verma et al., 1989). Comparing to Jun/Jun homodimer, the Jun/Fos heterodimer is a much more stable complex with enhanced DNA-binding and increased transcriptional activity (Chiu et al., 1988; Halazonetis et al., 1988; Kouzarides and Ziff, 1988; Cohen et al., 1989; Zerial et al., 1989; Angel et al., 1989). Hence, although different dimers bind common target sites on DNA, they do not necessarily result in equivalent transcriptional responses. In fact, of the multiple protein complexes that form in a given cellular environment, some activate transcription while others that bind to the same site may repress it. For example, Jun B may dimerizes with Fos and prevent c-Jun/Fos dimer formation. Because JunB differs from c-Jun in amino acid sequences within the DNA-binding and dimerization motif, the JunB-Fos dimer has a much decreased DNA binding activity. In the presence of JunB, c-Jun mediated trans-activation and transformation are significantly attenuated (Chiu et al., 1989; Schutte et al., 1989; Deng and Karin, 1993). c-Jun can form dimers as well with other members of the Fos family, such as Fra-1 and Fra-2, and can dimerize with several bZIP proteins of the AP-1 family, including the ATF and Maf proteins (Fig.13.1) (Cohen et al., 1989). Since different dimers have unique DNA binding specificity, dimerization with diverse partners greatly expands the regulatory potential of c-Jun (Chatton et al., 1993; Hai and Curran, 1991; Kataoka et al., 1994).

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