The mitotic checkpoint protein hBUB3 and the mRNA export factor hRAE1 interact with GLE2p-binding sequence (GLEBS)-containing proteins
Authors: M H Gazi
J M Harden
T J Yen
P C de Groen
J R Babu
W L Lingle
J M van Deursen
X Wang
S A Jablonski
Journal: Journal of Biological Chemistry (2001)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: mRNA export factor; RAE1; GLE2; mitotic checkpoint protein; BUB3
Affiliations: Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.

Abstract:  The mRNA export factor RAE1 (also called GLE2) and the mitotic checkpoint protein BUB3 share extensive sequence homology in yeast as well as higher eukaryotes, although the biological relevance of their similarity is unclear. Previous work in HeLa cells has shown that human (h)RAE1 binds the nuclear pore complex protein hNUP98 via a short NUP98 motif called GLEBS (for GLE2p-binding sequence). Here we report that the two known binding partners of hBUB3, the mitotic checkpoint proteins hBUB1 and hBUBR1, both carry a region with remarkable similarity to the GLEBS motif of hNUP98. We show that the GLEBS-like motifs of mouse (m)BUB1 and mBUBR1 are sufficient for mBUB3 binding. mBUB3 lacks affinity for the hNUP98 GLEBS, demonstrating its binding specificity for GLEBS motifs of mitotic checkpoint proteins. Interestingly, mRAE1 does not exclusively bind to the GLEBS motif of hNUP98 and can cross-interact with the mBUB1 GLEBS. We show that full-length RAE1 and BUB1 proteins interact in mammalian cells and accumulate both at the kinetochores of prometaphase chromosomes. Our findings demonstrate that GLEBS motifs reside in mammalian nucleoporins and mitotic checkpoint proteins and apparently serve as specific binding sites for either BUB3, RAE1, or both. 

Retracted: No

PubPeer comments:
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 Unreg......Agree. ....There are major issues with this paper The validation set shows almost half of the responders having deletions. How is this validated? Its random. about 50% of the responders have the  loss events and 70% of the nonresponders. This is not a valid. , 
 This is the same unreg as above. New paper from Tim Chan s group:  No recurrent copy-number alterations as determined by TCGA associated with response; nor did copy-number alterations in interferon (IFN) genes on chromosome 9p . http: www.cell.com cell pdf S0092-8674(17)31122-4.pdf Not a definitive refutation, but suggestive. , 
 James P. Allison, the scientist  behind game-changing cancer immunotherapies win Nobel medicine prize https: www.yahoo.com news 2018-nobel-medicine-prize-awarded-cancer-research-094355354.html , 
 I am not one of the authors.****I am not one of the authors. These comments from unregistered user are not important. The study in Cell revealed that loss of IFNG pathway is associated with resistance to anti-CTLA4. This makes a lot of sense since MHC-1 is upregulated by IFNG, and T cells need MHC-I on tumor cells to recognize them. Did someone ever knock out the murine Jak1 gene from the MC38 cell line and find that such tumors are resistant to anti-CTLA4? MC38 wild type responds to anti-CTLA4. So this mouse model would support the conclusion of the Cell paper. ,