Signal-peptide-mediated translocation is regulated by a p97-AIRAPL complex

Tal Glinka, Joel Alter, Ilana Braunstein, Lolita Tzach, Chia Wei Sheng, Susana Geifman, Mariola J. Edelmann, Benedikt M. Kessler, Ariel Stanhill

Research output: Contribution to journalArticlepeer-review


Protein homoeostasis is a fundamental requirement for all living cells in order to survive in a dynamic surrounding. Proper levels of AIRAPL (arsenite-inducible RNA-associated proteinlike protein) (ZFAND2B) are required in order to maintain cellular folding capacity in metazoans, and functional impairment of AIRAPL results in acceleration of aging and protein aggregation. However, the cellular roles of AIRAPL in this process are not known. In the present paper, we report that AIRAPL binds and forms a complex with p97 [VCP (valosin-containing protein)/Cdc48],Ubxd8 (ubiquitin regulatoryXdomain 8), Npl4- Ufd1, Derlin-1 and Bag6 on the ER (endoplasmic reticulum) membrane. In spite of the fact that AIRAPL complex partners are involved in the ERAD (ER-associated degradation) process, AIRAPL knockdown does not show any impairment in ERAD substrate degradation. However, translocation into the ER of a subset of ERAD- and non-ERAD-secreted proteins are regulated by AIRAPL. The ability to regulate translocation by the p97- AIRAPL complex is entirely dependent on the proteins' signal peptide. Our results demonstrate a p97 complex regulating translocation into the ER in a signal-peptide-dependent manner.

Original languageEnglish
Pages (from-to)253-261
Number of pages9
JournalBiochemical Journal
Issue number2
StatePublished - 15 Jan 2014
Externally publishedYes


  • Arsenite-inducible RNA-associated protein-like protein (AIRAPL)
  • Endoplasmic reticulum translocation
  • P97
  • Quality control
  • Signal peptide


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