Article

A domain within the tumor suppressor protein APC shows very similar biochemical properties as the microtubule-associated protein tau.

Arbeitsgruppe Tumorgenetik, Abteilung Strukturelle Biologie, Max-Planck-Institut für molekulare Physiologie, Dortmund, Germany.
European Journal of Biochemistry (impact factor: 3.58). 06/1998; 253(3):591-7. pp.591-7
Source: PubMed

ABSTRACT The tumor-suppressor protein APC (adenomatous polyposis coli) binds to microtubules and promotes tubulin assembly. In vivo the endogenous APC protein is mainly localized at the end of microtubules that are involved in active cell migration. Since most tumor-specific APC gene mutations lead to the loss of the microtubule binding domain this interaction is assumed to play a crucial role in tumorigenesis. In this study we show that an APC protein fragment (amino acids 2219-2580) within the C-terminal part is enough to bind to non-assembled tubulin with high affinity. The binding of APC to tubulin does not lead to an alteration of the intrinsic GTPase activity of the non-assembled tubulin. The APC protein induces the tubulin assembly in a fast reaction and below the critical assembly concentration of tubulin. The APC protein induces the bundling of the assembled microtubules in a concentration-dependent manner. Regarding its biochemical properties the analysed APC protein fragment strikingly resembles the members of the microtubule-associated protein family tau. This analogy may help to understand the role of the APC protein in the suppression of tumorigenesis.

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Keywords

active cell migration
 
adenomatous polyposis coli
 
analysed APC protein fragment
 
APC protein induces
 
assembled microtubules
 
bundling
 
C-terminal part
 
concentration-dependent manner
 
critical assembly concentration
 
endogenous APC protein
 
fast reaction
 
intrinsic GTPase activity
 
microtubule binding domain
 
non-assembled tubulin
 
promotes tubulin assembly
 
tubulin
 
tubulin assembly
 
tumor-specific APC gene mutations lead
 
tumor-suppressor protein APC
 
tumorigenesis
 

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