SENP1 participates in the dynamic regulation of Elk-1 sumoylation.
Résumé
The modification of proteins with SUMO plays an important role in determining their functional properties. Importantly though, sumoylation is a highly dynamic process enabling transient responses to be elicited. This dynamism is controlled by two competing conjugating and deconjugating activities. The latter activity is mediated by the SENP family of SUMO-specific proteases. The transcription factor Elk-1 undergoes rapid desumoylation following cellular stimulation with growth factors, and this contributes to its conversion from a SUMO-dependent repressor to a potent transcriptional activator. Here we demonstrate an important role for SENP1 in the desumoylation of Elk-1 and therefore an integral role in determining the Elk-1-dependent transcriptional programme. Amongst the SENPs, Elk-1 preferentially forms a complex with SENP1. This preferential binding is reflected by the higher efficiency of SENP1 in promoting Elk-1 transactivation. Moreover, depletion of SENP1 causes a reciprocal effect and reduces the transactivation properties of Elk-1. Partial redundancy of function with SENP2 is revealed by combinatorial knockdown studies. Importantly, depletion of SENP1 also reduces the activation of the Elk-1 target gene, c-FOS. Together, these results therefore reveal an important role of SENP1 in the regulation of Elk-1-mediated gene expression in response to mitogenic signaling cues.
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