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First published online September 18, 2007
doi: 10.1242/10.1242/jcs.010389

Journal of Cell Science 120, 3163-3172 (2007)
Published by The Company of Biologists 2007
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The RASSF1A tumor suppressor

Howard Donninger1, Michele D. Vos2 and Geoffrey J. Clark1,*

1 Molecular Targets Group, Department of Medicine, J. G. Brown Cancer Center, University of Louisville, 119C Baxter Boulevard, 580 S. Preston Street, Louisville, KY 40202, USA
2 Research Analysis and Evaluation Branch, NCI, Rockville, MD, USA


Figure 1
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  		Fig. 1. Summary of some of the known partners and pathways of RASSF1A. RASSF1A binds to at least three microtubule-binding proteins (MAPs), complexes with microtubules and regulates mitosis, the cell cycle and apoptosis in response to mitogenic or apoptotic stimuli. Direct interaction between RASSF1A and microtubule-associated proteins localizes RASSF1A to the microtubules, stabilizing them and, thereby, regulating mitosis. Repression of cyclins A and D1 by RASSF1A results in cell cycle arrest and interactions with CNK1, MST1, Salvador and MOAP1 may allow RASSF1A to modulate apoptosis.

 

Figure 2
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  		Fig. 2. RASSF1 gene locus and domain structure of the different RASSF1 isoforms. (A) The RASSF1 gene locus is characterized by eight exons (boxed regions) and two different promoters (arrows) with two associated CpG islands (black bars). Black boxes represent coding regions and white boxes are non-coding regions. (B) Schematic representation of the different RASSF1 isoforms. C1/DAG, conserved region 1 diacylglycerol-binding domain; ATM, ATM-kinase consensus phosphorylation sequence; RA, RalGDS/AF6 Ras association domain; SARAH, Sav/RASSF/Hpo interaction domain. The position of each domain (as outlined in the Swiss-Prot/TrEMBL database) is indicated above each isoform and the number of amino acids in each isoform is shown on the right.

 

Figure 3
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  		Fig. 3. RASSF1A binds Ras. (A) HEK-293-T cells were transfected with FLAG-tagged RASSF1A and HA-tagged forms of K-Ras12v. The cells were lysed and immunoprecipitated (IP) before being immunoblotted (IB) with HA and FLAG. Upper panel shows immunoprecipitation, lower panel shows protein levels in the cell lysate. Wild-type K-Ras, a Y40C effector mutant of K-Ras12v and a farnesylation-defective mutant of K-Ras12v (K-RasCX) were defective for binding RASSF1A.

 

Figure 4
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  		Fig. 4. RASSF1A associates with microtubules and localizes to centrosome and spindles during mitosis. COS cells were transfected with GFP-RASSF1A and the nuclei stained blue with DAPI.

 




© The Company of Biologists Ltd 2007