Teixeira FR, Manfiolli AO, Soares CS, Baqui MM, Koide T, Gomes MD

FBXO25 is one of the sixty-nine known human F-box proteins that serve as specificity factors for a family of ubiquitin ligases composed of SKP1, Rbx1, Cullin1 and F-box protein (SCF1) that are involved in targeting proteins for degradation across the ubiquitin proteasome system (UPS). However, the substrates of most SCF ...

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E3 ligases remain unknown. Here, we applied an in chip ubiquitination screen using a human protein microarray to uncover putative substrates for the FBXO25 protein. Among several novel putative targets identified, the c-Fos protooncogene regulator ELK-1 was characterized as the first endogenous substrate for SCF1(FBXO25) E3 ligase. The FBXO25 interacted with and mediated the ubiquitination and proteasomal degradation of ELK-1 in HEK293T cells. In addition, FBXO25 overexpression suppressed induction of two ELK-1 target genes, c-Fos and EGR-1, in response to PMA. Together, our findings show that FBXO25 mediates ELK-1 degradation through the UPS and thereby plays a role in regulating the activation of ELK-1 pathway in response to mitogens.

Date: Aug. 12, 2013

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