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A Wadle

Publications and source records attributed to A Wadle.

3 recordsLinked to original sources

Chromosomal localization and promoter analysis of the adenomatous polyposis coli binding protein RP1.

The EB1/RP1 family is a new protein family that is characterized by the ability of its members to serve as interacting partners for the adenomatous polyposis coli (APC) tumour suppressor protein and tubulin. Data obtained with highly conserved yeast homologues suggest that the EB1/RP1 protein family promotes cytoplasmic microtubule dynamics and contributes to the sensor mechanism controlling the cytokinesis checkpoint during mitosis. However, the precise function of this protein family in mammalian cells has not been elucidated so far and remains unclear. Here, we report on the genomic localization of the RP1 gene and the characterization of the corresponding promoter. The RP1 gene was found to be encoded on chromosome 18q21, a locus which is altered or deleted in up to 50% of all patients with colorectal cancer. Promoter analysis revealed that the RP1 gene is under the control of a strong promoter that was 10 times more active in mammalian cells when compared to SV40 promoter. Members of the cyclic AMP response element binding protein family (CREB1 and CREB2) could be identified as transcription factors binding specifically within the RP1 promoter sequence.

Base Sequence↗

EB/RP gene family encodes tubulin binding proteins.

Mutations in the adenomatous polyposis coli (APC) gene are linked to the dysplastic transformation of colorectal polyps and represent an early step in the development of colorectal tumors. Ninety-four percent of all mutations result in the expression of a truncated APC protein lacking the C-terminal region. The C-terminal region of the APC protein may have a tumor suppressor function as its absence appears to be linked to the development of dysplastic lesions. Recently, we discovered and characterized a protein called RP1 which binds specifically to the C-terminal region of the APC protein. We show now that RP1 and the other known members of the EB/RP family (EB1 and RP3) also bind directly to tubulin, both in vitro and in vivo. Immunohistochemical analyses reveal a distinct staining pattern during interphase as well as an association of RP1/EB1 with mitotic microtubule structures. The previously described puncta of the APC protein at the leading edge of membrane protrusions contact microtubule fibers that contain RP1 or EB1.

Adenomatous Polyposis Coli↗