Proteomics

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Identification of regulators of polyploidization presents therapeutic targetsfor treatment of AMKL

ABSTRACT: Wen Q, Goldenson B, Silver SJ, Schenone M, Dancik V, Huang Z, Wang LZ, Lewis TA, An WF, Li X, Bray MA, Thiollier C, Diebold L, Gilles L, Vokes MS, Moore CB, Bliss-Moreau M, Verplank L, Tolliday NJ, Mishra R, Vemula S, Shi J, Wei L, Kapur R, Lopez CK, Gerby B, Ballerini P, Pflumio F, Gilliland DG, Goldberg L,Birger Y, Izraeli S, Gamis AS, Smith FO, Woods WG, Taub J, Scherer CA, Bradner JE, Goh BC, Mercher T,Carpenter AE, Gould RJ, Clemons PA, Carr SA, Root DE, Schreiber SL, Stern AM, Crispino JD. Cell. 2012 150:575-89. doi: 10.1016/j.cell.2012.06.032. PMCID: PMC3613864

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Steven A. Carr 

PROVIDER: MSV000078536 | MassIVE | Mon Jan 27 19:01:00 GMT 2014

REPOSITORIES: MassIVE

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Identification of regulators of polyploidization presents therapeutic targets for treatment of AMKL.

Wen Qiang Q   Goldenson Benjamin B   Silver Serena J SJ   Schenone Monica M   Dancik Vlado V   Huang Zan Z   Wang Ling-Zhi LZ   Lewis Timothy A TA   An W Frank WF   Li Xiaoyu X   Bray Mark-Anthony MA   Thiollier Clarisse C   Diebold Lauren L   Gilles Laure L   Vokes Martha S MS   Moore Christopher B CB   Bliss-Moreau Meghan M   Verplank Lynn L   Tolliday Nicola J NJ   Mishra Rama R   Vemula Sasidhar S   Shi Jianjian J   Wei Lei L   Kapur Reuben R   Lopez Cécile K CK   Gerby Bastien B   Ballerini Paola P   Pflumio Francoise F   Gilliland D Gary DG   Goldberg Liat L   Birger Yehudit Y   Izraeli Shai S   Gamis Alan S AS   Smith Franklin O FO   Woods William G WG   Taub Jeffrey J   Scherer Christina A CA   Bradner James E JE   Goh Boon-Cher BC   Mercher Thomas T   Carpenter Anne E AE   Gould Robert J RJ   Clemons Paul A PA   Carr Steven A SA   Root David E DE   Schreiber Stuart L SL   Stern Andrew M AM   Crispino John D JD  

Cell 20120801 3

The mechanism by which cells decide to skip mitosis to become polyploid is largely undefined. Here we used a high-content image-based screen to identify small-molecule probes that induce polyploidization of megakaryocytic leukemia cells and serve as perturbagens to help understand this process. Our study implicates five networks of kinases that regulate the switch to polyploidy. Moreover, we find that dimethylfasudil (diMF, H-1152P) selectively increased polyploidization, mature cell-surface mar  ...[more]

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