Document Details

Document Type : Article In Journal 
Document Title :
RASSF1A Interacts with Microtubule-Associated Proteins and Modulates Microtubule Dynamics
RASSF1A Interacts with Microtubule-Associated Proteins and Modulates Microtubule Dynamics
 
Document Language : English 
Abstract : The candidate tumor suppressor gene RASSF1A is inactivated in many types of adult and childhood cancers. However, the mechanisms by which RASSF1A exerts its tumor suppressive functions have yet to be elucidated. To this end, we performed a yeast two-hybrid screen to identify novel RASSF1A-interacting proteins in a human brain cDNA library. Seventy percent of interacting clones had homology to microtubule-associated proteins, including MAP1B and VCY2IP1/C19ORF5. RASSF1A association with MAP1B and VCY2IP1/C19ORF5 was subsequently confirmed in mammalian cell lines. This suggested that RASSF1A may exert its tumor-suppressive functions through interaction with the microtubules. We demonstrate that RASSF1A associates with the microtubules, causing them to exist as hyperstabilized circular bundles. We found that two naturally occurring tumor-associated missense substitutions in the RASSF1A coding region, C65R and R257Q, perturb the association of RASSF1A with the microtubules. The C65R and R257Q in addition to VCY2IP1/C19ORF5 showed reduced ability to induce microtubule acetylation and were unable to protect the microtubules against the depolymerizing action of nocodazole. In addition, wild-type RASSF1A but not the C65R or the R257Q is able to block DNA synthesis. Our data identify a role for RASSF1A in the regulation of microtubules and cell cycle dynamics that could be part of the mechanism(s) by which RASSF1A exerts its growth inhibition on cancer cells. 
ISSN : 1538-7445 
Journal Name : CANCER RESEARCH 
Volume : 64 
Issue Number : 12 
Publishing Year : 1425 AH
2004 AD 
Article Type : Article 
Added Date : Monday, April 26, 2010 

Researchers

Researcher Name (Arabic)Researcher Name (English)Researcher TypeDr GradeEmail
فريدة لطيفLatif, Farida InvestigatorDoctorateflatif@hgmp.mrc.ac.uk
أشرف دلولDallol, Ashraf ResearcherDoctorate 

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