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Alterations to O‐GlcNAc cycling disrupt mitotic phosphorylation (555.16)
Author(s) -
Whelan Stephen,
Tan Ee Phie,
Costello Catherine,
McComb Mark,
Slawson Chad
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.555.16
Subject(s) - mitosis , phosphorylation , microbiology and biotechnology , regulator , serine , threonine , biology , spindle apparatus , function (biology) , cell cycle , chemistry , cell division , biochemistry , cell , gene
O‐GlcNAc is a post‐translational modification (PTM) consisting of a single N‐acetylglucosamine moiety attached to serine and threonine residues in nuclear and cytoplasmic proteins. O‐GlcNAc levels can cycle dynamically in response to hormones, nutrients, or stress in order to regulate a multitude of cellular processes. For instance O‐GlcNAc cycling is an important regulator of mitosis. Recently, we demonstrated that cells with a gain of function in either O‐GlcNAc transferase (OGT) or O‐GlcNAcase (OGA) have disrupted mitotic spindles and mitotic exit defects. OGT/OGA gain of function caused the formation of large poorly condensed spindle chromosomes, misaligned kinetochores, and an increase in multipolar spindles. This phenotype was caused partially by a disruption in phosphorylation. In this current study, our objective is to determine how alterations in O‐GlcNAc cycling disrupt mitotic phosphorylation cascades. We employed quantitative proteomics in order to identify changes to mitotic phosphorylation. We were able to quantitate both protein expression changes as well as alterations in PTM’s in OGT or OGA gain of function cells. We identified over 1000 proteins whose expression as well as PTM status was altered by aberrant O‐GlcNAcylation. These results demonstrate the cross‐talk between protein modifications involved in regulating mitotic progression and suggest that diseases that disrupt one PTM will also alter the actions of other PTM’s. Grant Funding Source : NIH‐NHLBI Contracts: HHSN268201000031C ‐ CPC; NIH Grants: P41 RR010888/GM104603 – MSR R21 HL107993 ;