This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dong, S.
Right arrow Articles by Tweardy, D. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dong, S.
Right arrow Articles by Tweardy, D. J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2004, p. 4465-4475, Vol. 24, No. 10
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.10.4465-4475.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Reduced Intranuclear Mobility of APL Fusion Proteins Accompanies Their Mislocalization and Results in Sequestration and Decreased Mobility of Retinoid X Receptor {alpha}

Shuo Dong,1,2 David L. Stenoien,3 Jihui Qiu,1 Michael A. Mancini,3 and David J. Tweardy1*

Section of Infectious Disease, Department of Medicine,1 Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030,3 Shanghai Institute of Hematology, Shanghai Rui-Jin Hospital, Shanghai 200025, People's Republic of China2

Received 30 October 2003/ Returned for modification 13 January 2004/ Accepted 12 February 2004

Acute promyelocytic leukemia (APL) cells contain one of five chimeric retinoic acid {alpha}-receptor (RAR{alpha}) genes (X-RAR{alpha}) created by chromosomal translocations or deletion; each generates a fusion protein thought to transcriptionally repress RAR{alpha} target genes and block myeloid differentiation by an incompletely understood mechanism. To gain spatiotemporal insight into these oncogenic processes, we employed fluorescence microscopy and fluorescence recovery after photobleaching (FRAP). Fluorescence microscopy demonstrated that the intracellular localization of each of the X-RAR{alpha} proteins was distinct from that of RAR{alpha} and established which portion(s) of each X-RAR{alpha} protein—X, RAR, or both—contributed to its altered localization. Using FRAP, we demonstrated that the intranuclear mobility of each X-RAR{alpha} was reduced compared to that of RAR{alpha}. In addition, the mobility of each X-RAR{alpha} was reduced further by ligand addition, in contrast to RAR{alpha}, which showed no change in mobility when ligand was added. Both the reduced baseline mobility of X-RAR{alpha} and the ligand-induced slowing of X-RAR{alpha} could be attributed to the protein interaction domain contained within X. RXR{alpha} aberrantly colocalized within each X-RAR{alpha}; colocalization of RXR{alpha} with promyelocytic leukemia (PML)-RAR{alpha} resulted in reduced mobility of RXR{alpha}. Thus, X-RAR{alpha} may interfere with RAR{alpha} through its aberrant nuclear dynamics, resulting in spatial and temporal sequestration of RXR{alpha} and perhaps other nuclear receptor coregulators critical for myeloid differentiation.

* Corresponding author. Mailing address: Section of Infectious Disease, Department of Medicine, Baylor College of Medicine, One Baylor Plaza, BCM 286, Room N1319, Houston, TX 77030. Phone: (713) 798-8918. Fax: (713) 798-8948. E-mail: dtweardy{at}bcm.tmc.edu.

Molecular and Cellular Biology, May 2004, p. 4465-4475, Vol. 24, No. 10
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.10.4465-4475.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Qiu, J. J., Lu, X., Zeisig, B. B., Ma, Z., Cai, X., Chen, S., Gronemeyer, H., Tweardy, D. J., So, C. W. E., Dong, S. (2010). Leukemic transformation by the APL fusion protein PRKAR1A-RAR{alpha} critically depends on recruitment of RXR{alpha}. Blood 115: 643-652 [Abstract] [Full Text]  
  • Weidtkamp-Peters, S., Lenser, T., Negorev, D., Gerstner, N., Hofmann, T. G., Schwanitz, G., Hoischen, C., Maul, G., Dittrich, P., Hemmerich, P. (2008). Dynamics of component exchange at PML nuclear bodies. J. Cell Sci. 121: 2731-2743 [Abstract] [Full Text]  
  • Huang, Y., Qiu, J., Dong, S., Redell, M. S., Poli, V., Mancini, M. A., Tweardy, D. J. (2007). Stat3 Isoforms, {alpha} and , Demonstrate Distinct Intracellular Dynamics with Prolonged Nuclear Retention of Stat3 Mapping to Its Unique C-terminal End. J. Biol. Chem. 282: 34958-34967 [Abstract] [Full Text]  
  • Qiu, J., Huang, Y., Chen, G., Chen, Z., Tweardy, D. J., Dong, S. (2007). Aberrant Chromatin Remodeling by Retinoic Acid Receptor {alpha} Fusion Proteins Assessed at the Single-Cell Level. Mol. Biol. Cell 18: 3941-3951 [Abstract] [Full Text]  
  • Campbell, E. M., Dodding, M. P., Yap, M. W., Wu, X., Gallois-Montbrun, S., Malim, M. H., Stoye, J. P., Hope, T. J. (2007). TRIM5{alpha} Cytoplasmic Bodies Are Highly Dynamic Structures. Mol. Biol. Cell 18: 2102-2111 [Abstract] [Full Text]  
  • Yasmin, R., Williams, R. M., Xu, M., Noy, N. (2005). Nuclear Import of the Retinoid X Receptor, the Vitamin D Receptor, and Their Mutual Heterodimer. J. Biol. Chem. 280: 40152-40160 [Abstract] [Full Text]  
  • Feige, J. N., Gelman, L., Tudor, C., Engelborghs, Y., Wahli, W., Desvergne, B. (2005). Fluorescence Imaging Reveals the Nuclear Behavior of Peroxisome Proliferator-activated Receptor/Retinoid X Receptor Heterodimers in the Absence and Presence of Ligand. J. Biol. Chem. 280: 17880-17890 [Abstract] [Full Text]  
  • Di Croce, L. (2005). Chromatin modifying activity of leukaemia associated fusion proteins. Hum Mol Genet 14: R77-R84 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»