Targeting protein for Xenopus kinesin-like protein 2 (TPX2) regulates γ-Histone 2AX (γ-H2AX) levels upon ionizing radiation
The microtubule-associated protein targeting protein for Xenopus kinesin-like protein 2 (TPX2) plays a key role in spindle assembly and is required for mitosis in human cells. In interphase, TPX2 is actively imported into the nucleus to prevent its premature activity in microtubule organization. To...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
October 8, 2012
|
| In: |
The journal of biological chemistry
Year: 2012, Volume: 287, Issue: 50, Pages: 42206-42222 |
| ISSN: | 1083-351X |
| DOI: | 10.1074/jbc.M112.385674 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1074/jbc.M112.385674 Verlag, Volltext: http://www.jbc.org/content/287/50/42206 
|
| Author Notes: | Gernot Neumayer, Angela Helfricht, Su Yeon Shim, Hoa Thi Le, Cecilia Lundin, Camille Belzil, Mathieu Chansard, Yaping Yu, Susan P. Lees-Miller, Oliver J. Gruss, Haico van Attikum, Thomas Helleday, and Minh Dang Nguyen |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1572600853 | ||
| 003 | DE-627 | ||
| 005 | 20230426124313.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 180503s2012 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1074/jbc.M112.385674 |2 doi | |
| 035 | |a (DE-627)1572600853 | ||
| 035 | |a (DE-576)502600853 | ||
| 035 | |a (DE-599)BSZ502600853 | ||
| 035 | |a (OCoLC)1341008227 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 32 |2 sdnb | ||
| 100 | 1 | |a Neumayer, Gernot |e VerfasserIn |0 (DE-588)1157043976 |0 (DE-627)1020044713 |0 (DE-576)502600756 |4 aut | |
| 245 | 1 | 0 | |a Targeting protein for Xenopus kinesin-like protein 2 (TPX2) regulates γ-Histone 2AX (γ-H2AX) levels upon ionizing radiation |c Gernot Neumayer, Angela Helfricht, Su Yeon Shim, Hoa Thi Le, Cecilia Lundin, Camille Belzil, Mathieu Chansard, Yaping Yu, Susan P. Lees-Miller, Oliver J. Gruss, Haico van Attikum, Thomas Helleday, and Minh Dang Nguyen |
| 264 | 1 | |c October 8, 2012 | |
| 300 | |a 17 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 03.05.2018 | ||
| 520 | |a The microtubule-associated protein targeting protein for Xenopus kinesin-like protein 2 (TPX2) plays a key role in spindle assembly and is required for mitosis in human cells. In interphase, TPX2 is actively imported into the nucleus to prevent its premature activity in microtubule organization. To date, no function has been assigned to nuclear TPX2. We now report that TPX2 plays a role in the cellular response to DNA double strand breaks induced by ionizing radiation. Loss of TPX2 leads to inordinately strong and transient accumulation of ionizing radiation-dependent Ser-139-phosphorylated Histone 2AX (γ-H2AX) at G0 and G1 phases of the cell cycle. This is accompanied by the formation of increased numbers of high intensity γ-H2AX ionizing radiation-induced foci. Conversely, cells overexpressing TPX2 have reduced levels of γ-H2AX after ionizing radiation. Consistent with a role for TPX2 in the DNA damage response, we found that the protein accumulates at DNA double strand breaks and associates with the mediator of DNA damage checkpoint 1 (MDC1) and the ataxia telangiectasia mutated (ATM) kinase, both key regulators of γ-H2AX amplification. Pharmacologic inhibition or depletion of ATM or MDC1, but not of DNA-dependent protein kinase (DNA-PK), antagonizes the γ-H2AX phenotype caused by TPX2 depletion. Importantly, the regulation of γ-H2AX signals by TPX2 is not associated with apoptosis or the mitotic functions of TPX2. In sum, our study identifies a novel and the first nuclear function for TPX2 in the cellular responses to DNA damage. | ||
| 650 | 4 | |a Cell Cycle | |
| 650 | 4 | |a Cytoskeleton | |
| 650 | 4 | |a DNA Damage Response | |
| 650 | 4 | |a MAPs | |
| 650 | 4 | |a Mitosis | |
| 650 | 4 | |a Neurons | |
| 650 | 4 | |a TPX2 | |
| 700 | 1 | |a Gruss, Oliver |e VerfasserIn |0 (DE-588)1038251028 |0 (DE-627)757162541 |0 (DE-576)179138391 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The journal of biological chemistry |d [Amsterdam] : Elsevier B.V., 1905 |g 287(2012), 50, Seite 42206-42222 |h Online-Ressource |w (DE-627)269247025 |w (DE-600)1474604-9 |w (DE-576)077883837 |x 1083-351X |7 nnas |a Targeting protein for Xenopus kinesin-like protein 2 (TPX2) regulates γ-Histone 2AX (γ-H2AX) levels upon ionizing radiation |
| 773 | 1 | 8 | |g volume:287 |g year:2012 |g number:50 |g pages:42206-42222 |g extent:17 |a Targeting protein for Xenopus kinesin-like protein 2 (TPX2) regulates γ-Histone 2AX (γ-H2AX) levels upon ionizing radiation |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1074/jbc.M112.385674 |x Verlag |x Resolving-System |3 Volltext |
| 856 | 4 | 0 | |u http://www.jbc.org/content/287/50/42206 |x Verlag |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20180503 | ||
| 993 | |a Article | ||
| 994 | |a 2012 | ||
| 998 | |g 1038251028 |a Gruss, Oliver |m 1038251028:Gruss, Oliver |d 700000 |d 706000 |e 700000PG1038251028 |e 706000PG1038251028 |k 0/700000/ |k 1/700000/706000/ |p 10 | ||
| 999 | |a KXP-PPN1572600853 |e 3007858607 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"person":[{"given":"Gernot","family":"Neumayer","role":"aut","roleDisplay":"VerfasserIn","display":"Neumayer, Gernot"},{"given":"Oliver","family":"Gruss","role":"aut","roleDisplay":"VerfasserIn","display":"Gruss, Oliver"}],"title":[{"title":"Targeting protein for Xenopus kinesin-like protein 2 (TPX2) regulates γ-Histone 2AX (γ-H2AX) levels upon ionizing radiation","title_sort":"Targeting protein for Xenopus kinesin-like protein 2 (TPX2) regulates γ-Histone 2AX (γ-H2AX) levels upon ionizing radiation"}],"recId":"1572600853","language":["eng"],"type":{"bibl":"article-journal","media":"Online-Ressource"},"note":["Gesehen am 03.05.2018"],"name":{"displayForm":["Gernot Neumayer, Angela Helfricht, Su Yeon Shim, Hoa Thi Le, Cecilia Lundin, Camille Belzil, Mathieu Chansard, Yaping Yu, Susan P. Lees-Miller, Oliver J. Gruss, Haico van Attikum, Thomas Helleday, and Minh Dang Nguyen"]},"id":{"eki":["1572600853"],"doi":["10.1074/jbc.M112.385674"]},"origin":[{"dateIssuedKey":"2012","dateIssuedDisp":"October 8, 2012"}],"relHost":[{"id":{"zdb":["1474604-9"],"eki":["269247025"],"issn":["1083-351X"]},"origin":[{"publisher":"Elsevier B.V. ; American Soc. of Biological Chemists ; ASBMB Publications","dateIssuedKey":"2021","dateIssuedDisp":"2021-","publisherPlace":"[Amsterdam] ; Baltimore, Md. [u.a.] ; Bethesda, Md."}],"name":{"displayForm":["publ. by the American Society for Biochemistry and Molecular Biology"]},"physDesc":[{"extent":"Online-Ressource"}],"title":[{"title":"The journal of biological chemistry","subtitle":"JBC","title_sort":"journal of biological chemistry"}],"titleAlt":[{"title":"JBC online"},{"title":"JBC"}],"part":{"issue":"50","pages":"42206-42222","year":"2012","extent":"17","text":"287(2012), 50, Seite 42206-42222","volume":"287"},"pubHistory":["1.1905/06 -"],"language":["eng"],"corporate":[{"display":"American Society for Biochemistry and Molecular Biology","roleDisplay":"Herausgebendes Organ","role":"isb"}],"recId":"269247025","disp":"Targeting protein for Xenopus kinesin-like protein 2 (TPX2) regulates γ-Histone 2AX (γ-H2AX) levels upon ionizing radiationThe journal of biological chemistry","type":{"media":"Online-Ressource","bibl":"periodical"},"note":["Gesehen am 19.05.2021"]}],"physDesc":[{"extent":"17 S."}]} | ||
| SRT | |a NEUMAYERGETARGETINGP8201 | ||