Axel Behrens

Mammalian Genetics Laboratory

Cellular responses to extracellular signals are mediated by changes in transcription factor activity and subsequent modulation of target gene expression. The proto-oncoprotein c-Jun belongs to the AP-1 group of transcription factors, which is a key regulator of cellular proliferation, apoptosis and tumorigenesis. AP-1 stimulation is mediated, in part, by the phosphorylation of c-Jun by the Jun N-terminal kinases (JNKs)¹. We have shown that the JNK/c-Jun pathway is required for clinically important diseases including neurodegenerative insults and cancer^{2 - 4}.

To investigate the mechanism of JNP-mediated transcriptional regulation, we have recently developed a novel methodology to identify proteins that interact with c-Jun in a phosphorylation-dependent manner⁵. The novel c-Jun interactors we identified (PDJs) have several different biological activities, ranging from transcriptional cofactors to chromatin modifyers. We would like to characterise PDJ function using in vitro approaches and the generation of PDJ mouse models, focussing on the nervous and hematopoietic system.

Therefore a postdoctoral fellow with interest and experience in neurobiology and/or immunology is sought to characterise the biological activities of these newly identified regulators of JNK signalling.

References

1. Chang L and Karin M Nature 2001; 410, 37-40.
2. Behrens A et al. Nat Genet 1999; 21, 326-9.
3. Behrens A et al. Oncogene 2000; 19, 2657-63.
4. Raivich G et al. Neuron 2004; 43, 57-67.
5. Nateri AS et al. Science 2004; 303, 1374-8.