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TPX2: of spindle assembly, DNA damage response, and cancer

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Abstract

For more than 15 years, TPX2 has been studied as a factor critical for mitosis and spindle assembly. These functions of TPX2 are attributed to its Ran-regulated microtubule-associated protein properties and to its control of the Aurora A kinase. Overexpressed in cancers, TPX2 is being established as marker for the diagnosis and prognosis of malignancies. During interphase, TPX2 resides preferentially in the nucleus where its function had remained elusive until recently. The latest finding that TPX2 plays a role in amplification of the DNA damage response, combined with the characterization of TPX2 knockout mice, open new perspectives to understand the biology of this protein. This review provides an historic overview of the discovery of TPX2 and summarizes its cytoskeletal and signaling roles with relevance to cancer therapies. Finally, the review aims to reconcile discrepancies between the experimental and pathological effects of TPX2 overexpression and advances new roles for compartmentalized TPX2.

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Abbreviations

APC/C:

Anaphase-promoting complex/cyclosome

ATM:

Ataxia telangiectasia mutated

GEF:

Guanine nucleotide exchange factor

GTPase:

Guanosine tri-phosphatase

HURP:

Hepatocarcinoma upregulated

K-fibres:

Kinetochore-fibers

MT:

Microtubule

MAP:

Microtubule-associated protein

MEFs:

Mouse embryonic fibroblasts

NLS:

Nuclear localization signal

PP1:

Protein phosphatase 1

RanGAP:

RanGTPase-activating protein

RanBP1+2:

Ran binding protein 1+2

RCC1:

Regulator of chromosome condensation 1

TPX2:

Targeting protein for Xklp2

ULMS:

Uterine leiomyosarcoma

Wt:

Wild-type

Xklp2:

Xenopus kinesin-like protein 2

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Acknowledgments

MD Nguyen receives support from the Canadian Institutes of Health Research (CIHR) and Alberta Innovates-Health Solutions (AIHS). G Neumayer received a DOC-scholarship from the Austrian Academy of Sciences at the University of Calgary, an Achievers in Medical Sciences recruitment award at the University of Calgary and a scholarship from the Alberta Cancer Foundation. C Belzil receives a AIHS studentship and a Ted Fong/Hotchkiss Brain Institute doctoral scholarship at the University of Calgary.

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Correspondence to Minh Dang Nguyen.

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G. Neumayer is the co-corresponding author

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Neumayer, G., Belzil, C., Gruss, O.J. et al. TPX2: of spindle assembly, DNA damage response, and cancer. Cell. Mol. Life Sci. 71, 3027–3047 (2014). https://doi.org/10.1007/s00018-014-1582-7

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  • DOI: https://doi.org/10.1007/s00018-014-1582-7

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