Protein DDI1 homolog 2

Definition:

Aspartic protease that mediates the cleavage of NFE2L1/NRF1 at 'Leu-104', thereby promoting release of NFE2L1/NRF1 from the endoplasmic reticulum membrane. Ubiquitination of NFE2L1/NRF1 is a prerequisite for cleavage, suggesting that DDI2 specifically recognizes and binds ubiquitinated NFE2L1/NRF1. Seems to act as a proteasomal shuttle which links the proteasome and replication fork proteins like RTF2 (Probable). Required, with DDI1, for cellular survival following replication stress. Together or redudantly with DDI1, removes RTF2 from stalled forks to allow cell cycle progression after replication stress and maintains genome integrity.

References:

[1]. Shun Koizumi, et al. The aspartyl protease DDI2 activates Nrf1 to compensate for proteasome dysfunction. Elife. 2016 Aug 16;5:e18357. [Content Brief]

[2]. Molly C Kottemann, et al. Removal of RTF2 from Stalled Replisomes Promotes Maintenance of Genome Integrity. Mol Cell. 2018 Jan 4;69(1):24-35.e5. [Content Brief]

[3]. Zhe Sha, et al. Reply to Vangala et al.: Complete inhibition of the proteasome reduces new proteasome production by causing Nrf1 aggregation. Curr Biol. 2016 Sep 26;26(18):R836-R837. [Content Brief]

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