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Published November 18, 2014 | Supplemental Material + Published
Journal Article Open

Liat1, an arginyltransferase-binding protein whose evolution among primates involved changes in the numbers of its 10-residue repeats


The arginyltransferase Ate1 is a component of the N-end rule pathway, which recognizes proteins containing N-terminal degradation signals called N-degrons, polyubiquitylates these proteins, and thereby causes their degradation by the proteasome. At least six isoforms of mouse Ate1 are produced through alternative splicing of Ate1 pre-mRNA. We identified a previously uncharacterized mouse protein, termed Liat1 (ligand of Ate1), that interacts with Ate1 but does not appear to be its arginylation substrate. Liat1 has a higher affinity for the isoforms Ate1^(1A7A) and Ate1^(1B7A). Liat1 stimulated the in vitro N-terminal arginylation of a model substrate by Ate1. All examined vertebrate and some invertebrate genomes encode proteins sequelogous (similar in sequence) to mouse Liat1. Sequelogs of Liat1 share a highly conserved ∼30-residue region that is shown here to be required for the binding of Liat1 to Ate1. We also identified non-Ate1 proteins that interact with Liat1. In contrast to Liat1 genes of nonprimate mammals, Liat1 genes of primates are subtelomeric, a location that tends to confer evolutionary instability on a gene. Remarkably, Liat1 proteins of some primates, from macaques to humans, contain tandem repeats of a 10-residue sequence, whereas Liat1 proteins of other mammals contain a single copy of this motif. Quantities of these repeats are, in general, different in Liat1 of different primates. For example, there are 1, 4, 13, 13, 17, and 17 repeats in the gibbon, gorilla, orangutan, bonobo, neanderthal, and human Liat1, respectively, suggesting that repeat number changes in this previously uncharacterized protein may contribute to evolution of primates.

Additional Information

© 2014 National Academy of Sciences. Contributed by Alexander Varshavsky, October 13, 2014 (sent for review October 6, 2014; reviewed by Wolfgang Baumeister and Avram Hershko). Published online before print November 4, 2014. We thank E. Udartseva for excellent technical assistance, and other members of the A.V. laboratory for their help and advice. This study was supported by the National Institutes of Health Grants DK039520 and GM031530 (to A.V.). Author contributions: C.S.B., C.E.R., and A.V. designed research; C.S.B., C.E.R., R.H.J., B.C.W., and K.I.P. performed research; B.C.W. and K.I.P. contributed new reagents/analytic tools; C.S.B., C.E.R., and A.V. analyzed data; and C.S.B., C.E.R., B.C.W., and A.V. wrote the paper. Reviewers included: W.B., Max Planck Institute of Biochemistry; and A.H., Technion Israel Institute of Technology. The authors declare no conflict of interest. This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. 1073/pnas.1419587111/-/DCSupplemental.

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Published - E4936.full.pdf

Supplemental Material - pnas.201419587SI.pdf


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August 22, 2023
October 18, 2023