Abstract
The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to proteins is an abundant and reversible modification that involves many cellular processes including transcription, translation, cell proliferation, apoptosis, and signal transduction. Here, we found that the O-GlcNAc modification pattern was altered during all-trans retinoic acid (tRA)-induced neurite outgrowth in the MN9D neuronal cell line. We identified several O-GlcNAcylated proteins using mass spectrometric analysis, including α- and β-tubulin. Further analysis of α- and β-tubulin revealed that O-GlcNAcylated peptides mapped between residues 173 and 185 of α-tubulin and between residues 216 and 238 of β-tubulin, respectively. We found that an increase in α-tubulin O-GlcNAcylation reduced heterodimerization and that O-GlcNAcylated tubulin did not polymerize into microtubules. Consequently, when O-GlcNAcase inhibitors were co-incubated with tRA, the extent of neurite outgrowth was decreased by 20% compared to control. Thus, our data indicate that the O-GlcNAcylation of tubulin negatively regulates microtubule formation.
| Original language | English |
|---|---|
| Pages (from-to) | 809-818 |
| Number of pages | 10 |
| Journal | Amino Acids |
| Volume | 40 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2011 Mar 1 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Clinical Biochemistry
- Organic Chemistry
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O-GlcNAcylation of tubulin inhibits its polymerization. / Ji, Suena; Kang, Jeong Gu; Park, Sang Yoon; Lee, Joohun; Oh, Young J.; Cho, Jin Won.
In: Amino Acids, Vol. 40, No. 3, 01.03.2011, p. 809-818.Research output: Contribution to journal › Article
TY - JOUR
T1 - O-GlcNAcylation of tubulin inhibits its polymerization
AU - Ji, Suena
AU - Kang, Jeong Gu
AU - Park, Sang Yoon
AU - Lee, Joohun
AU - Oh, Young J.
AU - Cho, Jin Won
PY - 2011/3/1
Y1 - 2011/3/1
N2 - The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to proteins is an abundant and reversible modification that involves many cellular processes including transcription, translation, cell proliferation, apoptosis, and signal transduction. Here, we found that the O-GlcNAc modification pattern was altered during all-trans retinoic acid (tRA)-induced neurite outgrowth in the MN9D neuronal cell line. We identified several O-GlcNAcylated proteins using mass spectrometric analysis, including α- and β-tubulin. Further analysis of α- and β-tubulin revealed that O-GlcNAcylated peptides mapped between residues 173 and 185 of α-tubulin and between residues 216 and 238 of β-tubulin, respectively. We found that an increase in α-tubulin O-GlcNAcylation reduced heterodimerization and that O-GlcNAcylated tubulin did not polymerize into microtubules. Consequently, when O-GlcNAcase inhibitors were co-incubated with tRA, the extent of neurite outgrowth was decreased by 20% compared to control. Thus, our data indicate that the O-GlcNAcylation of tubulin negatively regulates microtubule formation.
AB - The attachment of O-linked β-N-acetylglucosamine (O-GlcNAc) to proteins is an abundant and reversible modification that involves many cellular processes including transcription, translation, cell proliferation, apoptosis, and signal transduction. Here, we found that the O-GlcNAc modification pattern was altered during all-trans retinoic acid (tRA)-induced neurite outgrowth in the MN9D neuronal cell line. We identified several O-GlcNAcylated proteins using mass spectrometric analysis, including α- and β-tubulin. Further analysis of α- and β-tubulin revealed that O-GlcNAcylated peptides mapped between residues 173 and 185 of α-tubulin and between residues 216 and 238 of β-tubulin, respectively. We found that an increase in α-tubulin O-GlcNAcylation reduced heterodimerization and that O-GlcNAcylated tubulin did not polymerize into microtubules. Consequently, when O-GlcNAcase inhibitors were co-incubated with tRA, the extent of neurite outgrowth was decreased by 20% compared to control. Thus, our data indicate that the O-GlcNAcylation of tubulin negatively regulates microtubule formation.
UR - http://www.scopus.com/inward/record.url?scp=79954435787&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79954435787&partnerID=8YFLogxK
U2 - 10.1007/s00726-010-0698-9
DO - 10.1007/s00726-010-0698-9
M3 - Article
C2 - 20665223
AN - SCOPUS:79954435787
VL - 40
SP - 809
EP - 818
JO - Amino Acids
JF - Amino Acids
SN - 0939-4451
IS - 3
ER -