C-Fos Posttranslational Modifications

Sumoylation

The SUMO pathway resembles that of ubiquitin (24, 27, 36). It utilizes a single heterodimeric E1 SUMO-activating enzyme, Sae1/Sae2, and one E2 SUMO-conjugating enzyme, Ubc9. Although SUMO E1 and E2 are usually sufficient for sumoylation of substrates in vitro, a third component, E3, is also likely to be used in vivo for substrate selection and to ensure the specificity of reaction.

lysine 265

From Bossis et al 2005 PMID 16055710

Site

Conjugated by the peptidic posttranslational modifiers SUMO-1, SUMO-2, and SUMO-3.

"We noted that c-Fos contains a psi-KXE (where psi is a large hydrophobic residue, K the conjugated lysine, E glutamic acid, and X any amino acid) consensus motif (45) for conjugation by SUMO, a peptidic posttranslational modifier structurally related to ubiquitin and conjugated on acceptor lysines.

Effect

Decreases transcriptional activity of c-Fos/c-Jun dimers. "The lower activity of sumoylated c-Fos is not due to inhibition of protein entry into the nucleus, accelerated turnover, and intrinsic inability to dimerize or to bind to DNA. Instead, cell fractionation experiments suggest that decreased transcriptional activity of sumoylated c-Fos is associated with specific intranuclear distribution.

Regulation

Inhibited by phosphorylation (by an unknown kinase) at threonine 232

Erk1/2 and Rsk1/2 kinases in this process. The use of kinase inhibitors revealed no role for the Erk1/2 and Rsk1/2 kinases, or the phosphatidyl- inositol 3-kinase/Akt, Jnk, and P38/SAPK pathways in the reduction of c-Fos sumoylation.