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Monoubiquitination Promotes Calpain Cleavage of the Protein Phosphatase 2A (PP2A) Regulatory Subunit alpha 4, Altering PP2A Stability and Microtubule-associated Protein Phosphorylation

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Monoubiquitination Promotes Calpain Cleavage of the Protein Phosphatase 2A (PP2A) Regulatory Subunit alpha 4, Altering PP2A Stability and Microtubule-associated Protein Phosphorylation. / Watkins, Guy R.; Wang, Ning; Mazalouskas, Matthew D.; Gomez, Rey J.; Guthrie, Chris R.; Kraemer, Brian C.; Schweiger, Susann; Spiller, Benjamin W.; Wadzinski, Brian E.

In: Journal of Biological Chemistry, Vol. 287, No. 29, 13.07.2012, p. 24207-24215.

Research output: Contribution to journalArticle

Harvard

Watkins, GR, Wang, N, Mazalouskas, MD, Gomez, RJ, Guthrie, CR, Kraemer, BC, Schweiger, S, Spiller, BW & Wadzinski, BE 2012, 'Monoubiquitination Promotes Calpain Cleavage of the Protein Phosphatase 2A (PP2A) Regulatory Subunit alpha 4, Altering PP2A Stability and Microtubule-associated Protein Phosphorylation' Journal of Biological Chemistry, vol 287, no. 29, pp. 24207-24215.

APA

Watkins, G. R., Wang, N., Mazalouskas, M. D., Gomez, R. J., Guthrie, C. R., Kraemer, B. C., Schweiger, S., Spiller, B. W., & Wadzinski, B. E. (2012). Monoubiquitination Promotes Calpain Cleavage of the Protein Phosphatase 2A (PP2A) Regulatory Subunit alpha 4, Altering PP2A Stability and Microtubule-associated Protein Phosphorylation. Journal of Biological Chemistry, 287(29), 24207-24215doi: 10.1074/jbc.M112.368613

Vancouver

Watkins GR, Wang N, Mazalouskas MD, Gomez RJ, Guthrie CR, Kraemer BC et al. Monoubiquitination Promotes Calpain Cleavage of the Protein Phosphatase 2A (PP2A) Regulatory Subunit alpha 4, Altering PP2A Stability and Microtubule-associated Protein Phosphorylation. Journal of Biological Chemistry. 2012 Jul 13;287(29):24207-24215.

Author

Watkins, Guy R.; Wang, Ning; Mazalouskas, Matthew D.; Gomez, Rey J.; Guthrie, Chris R.; Kraemer, Brian C.; Schweiger, Susann; Spiller, Benjamin W.; Wadzinski, Brian E. / Monoubiquitination Promotes Calpain Cleavage of the Protein Phosphatase 2A (PP2A) Regulatory Subunit alpha 4, Altering PP2A Stability and Microtubule-associated Protein Phosphorylation.

In: Journal of Biological Chemistry, Vol. 287, No. 29, 13.07.2012, p. 24207-24215.

Research output: Contribution to journalArticle

Bibtex - Download

@article{35fd556c5f3d4d939186be000ddee9d0,
title = "Monoubiquitination Promotes Calpain Cleavage of the Protein Phosphatase 2A (PP2A) Regulatory Subunit alpha 4, Altering PP2A Stability and Microtubule-associated Protein Phosphorylation",
author = "Watkins, {Guy R.} and Ning Wang and Mazalouskas, {Matthew D.} and Gomez, {Rey J.} and Guthrie, {Chris R.} and Kraemer, {Brian C.} and Susann Schweiger and Spiller, {Benjamin W.} and Wadzinski, {Brian E.}",
year = "2012",
volume = "287",
number = "29",
pages = "24207--24215",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Monoubiquitination Promotes Calpain Cleavage of the Protein Phosphatase 2A (PP2A) Regulatory Subunit alpha 4, Altering PP2A Stability and Microtubule-associated Protein Phosphorylation

A1 - Watkins,Guy R.

A1 - Wang,Ning

A1 - Mazalouskas,Matthew D.

A1 - Gomez,Rey J.

A1 - Guthrie,Chris R.

A1 - Kraemer,Brian C.

A1 - Schweiger,Susann

A1 - Spiller,Benjamin W.

A1 - Wadzinski,Brian E.

AU - Watkins,Guy R.

AU - Wang,Ning

AU - Mazalouskas,Matthew D.

AU - Gomez,Rey J.

AU - Guthrie,Chris R.

AU - Kraemer,Brian C.

AU - Schweiger,Susann

AU - Spiller,Benjamin W.

AU - Wadzinski,Brian E.

PY - 2012/7/13

Y1 - 2012/7/13

N2 - <p>Multiple neurodegenerative disorders are linked to aberrant phosphorylation of microtubule-associated proteins (MAPs). Protein phosphatase 2A (PP2A) is the major MAP phosphatase; however, little is known about its regulation at microtubules. alpha 4 binds the PP2A catalytic subunit (PP2Ac) and the microtubule-associated E3 ubiquitin ligase MID1, and through unknown mechanisms can both reduce and enhance PP2Ac stability. We show MID1-dependent monoubiquitination of alpha 4 triggers calpain-mediated cleavage and switches alpha 4's activity from protective to destructive, resulting in increased Tau phosphorylation. This regulatory mechanism appears important in MAP-dependent pathologies as levels of cleaved alpha 4 are decreased in Opitz syndrome and increased in Alzheimer disease, disorders characterized by MAP hypophosphorylation and hyperphosphorylation, respectively. These findings indicate that regulated inter-domain cleavage controls the dual functions of alpha 4, and dysregulation of alpha 4 cleavage may contribute to Opitz syndrome and Alzheimer disease.</p>

AB - <p>Multiple neurodegenerative disorders are linked to aberrant phosphorylation of microtubule-associated proteins (MAPs). Protein phosphatase 2A (PP2A) is the major MAP phosphatase; however, little is known about its regulation at microtubules. alpha 4 binds the PP2A catalytic subunit (PP2Ac) and the microtubule-associated E3 ubiquitin ligase MID1, and through unknown mechanisms can both reduce and enhance PP2Ac stability. We show MID1-dependent monoubiquitination of alpha 4 triggers calpain-mediated cleavage and switches alpha 4's activity from protective to destructive, resulting in increased Tau phosphorylation. This regulatory mechanism appears important in MAP-dependent pathologies as levels of cleaved alpha 4 are decreased in Opitz syndrome and increased in Alzheimer disease, disorders characterized by MAP hypophosphorylation and hyperphosphorylation, respectively. These findings indicate that regulated inter-domain cleavage controls the dual functions of alpha 4, and dysregulation of alpha 4 cleavage may contribute to Opitz syndrome and Alzheimer disease.</p>

U2 - 10.1074/jbc.M112.368613

DO - 10.1074/jbc.M112.368613

M1 - Article

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 29

VL - 287

SP - 24207

EP - 24215

ER -

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