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p600/UBR4 in the central nervous system

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Abstract

A decade ago, the large 600 kDa mammalian protein p600 (also known as UBR4) was discovered as a multifunctional protein with roles in anoikis, viral transformation and protein degradation. Recently, p600 has emerged as a critical protein in the mammalian brain with roles in neurogenesis, neuronal migration, neuronal signaling and survival. How p600 integrates these apparently unrelated functions to maintain tissue homeostasis and murine survival remains unclear. The common molecular basis underlying many of the actions of p600 suggests, however, certain conservation and transposition of these functions across systems. In this review, we summarize the central nervous system functions of p600 and propose new perspectives on its biological complexity in neuronal physiology and neurological diseases.

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Abbreviations

a.a.:

Amino acid

ASD:

Autism spectrum disorder

BPV-1:

Bovine papillomavirus type 1

Ca2+ :

Calcium

CaM:

Calmodulin

CaMKIIα:

CaM-dependent protein Kinase II α isoform

CNS:

Central nervous system

ER:

Endoplasmic reticulum

FAK:

Focal adhesion kinase

hCALO:

Human homologue of Calossin

HPV-16:

Human papillomavirus type 16

MT:

Microtubule

N-cadherin:

Neuronal cadherin

p600:

Protein 600

RB:

Retinoblastoma protein

RBAF600:

Retinoblastoma-associated factor of 600 kDa

Ub:

Ubiquitin

UBR4:

Ubiquitin protein ligase E3 component N-recognin 4

ZUBR1:

Zinc finger UBR1 type 1

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Acknowledgments

The work on p600 is supported by the Canadian Institutes of Health Research (CIHR) (MDN) and Alberta Innovates Health Solutions (AIHS) (MDN). MDN held a Career Development Award from the Human Frontier Science Program Organization, a New Investigator Award from the CIHR and a Scholar Award from the AIHS. KP received an AIHS scholarship.

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Authors and Affiliations

  1. Department of Clinical Neurosciences, University of Calgary, Hotchkiss Brain Institute, 3330 Hospital Drive NW, Calgary, T2N 4N1, Canada

    Kari Parsons & Minh Dang Nguyen

  2. Department of Cell Biology and Anatomy, University of Calgary, Hotchkiss Brain Institute, 3330 Hospital Drive NW, Calgary, T2N 4N1, Canada

    Kari Parsons & Minh Dang Nguyen

  3. Department of Biochemistry and Molecular Biology, University of Calgary, Hotchkiss Brain Institute, 3330 Hospital Drive NW, Calgary, T2N 4N1, Canada

    Kari Parsons & Minh Dang Nguyen

  4. Dana Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA, 02215, USA

    Yoshihiro Nakatani

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  1. Kari Parsons
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  3. Minh Dang Nguyen
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Correspondence to Minh Dang Nguyen.

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Parsons, K., Nakatani, Y. & Nguyen, M.D. p600/UBR4 in the central nervous system. Cell. Mol. Life Sci. 72, 1149–1160 (2015). https://doi.org/10.1007/s00018-014-1788-8

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  • DOI: https://doi.org/10.1007/s00018-014-1788-8

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