A MHC-encoded ubiquitin-like protein (FAT10) binds noncovalently to the spindle assembly checkpoint protein MAD2

A MHC-encoded ubiquitin-like protein (FAT10) binds noncovalently to the spindle assembly checkpoint protein MAD2

^*Department of Genetics and ^‡Division of Cardiovascular Medicine, Internal Medicine, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06511; and ^†Genelogic Incorporated, Gaithersburg, MD 20878

Contributed by Sherman M. Weissman

Abstract

Recently a number of nonclass I genes were discovered in the human MHC class I region. One of these, FAT10, encodes a protein consisting of two domains with homology to ubiquitin. FAT10 mRNA is expressed constitutively in some lymphoblastoid lines and dendritic cells and in certain other cells after γ-interferon induction. FAT10 protein expression is controlled at several levels including transcription, translation, and protein stability. Yeast two-hybrid screening of a human lymphocyte library and immunoprecipitation studies revealed that FAT10 noncovalently associated with MAD2, a protein implicated in a cell-cycle checkpoint for spindle assembly during anaphase. Thus, FAT10 may modulate cell growth during B cell or dendritic cell development and activation.

Footnotes

↵ § To whom reprint requests should be addressed at: Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510. e-mail: Sherman.weissman{at}yale.edu.
ABBREVIATIONS:

UBL,

ubiquitin-like;

TNF,

tumor necrosis factor;

YAC,

yeast artificial chromosome;

ALLN,

acetyl-leucinyl-leucinal-norleucinal;

UTR,

untranslated region;

GST,

glutathione S-transferase;

MAD,

mitotic arrest deficiency;

uORF,

upstream ORF