[The involvement of c-Abl and D40 (AF15q14/CASC5) proteins in the regulation of cell proliferation and cancer].

Although c-Abl and D40 proteins are localized predominantly in nucleus, they are involved in different cellular processes. c-Abl is a tyrosine-kinase that takes part in protein phosphorylation on tyrosine. Recently D40 has been identified as a component of outer kinetochore complex. Despite of functional differences between c-Abl and D40 proteins, they have some similarities. First, high expression levels of c-Abl and D40 were observed not only in proliferating somatic cells, such as tumors, but also in healthy human testis. The increased expression levels of c-Abl and D40 protein in spermatocytes and acrosome of spermatids indicate their role in meiosis and spermatogenesis. Second, both proteins interact with specific regions of chromatin and are involved in the regulation of cell growth and division. Third, ABL and D40 (AF15q14) genes are involved in chromosomal translocations that subsequently form chimeric oncoproteins BCR-ABL, TEL-ABL and MLL-AF15q14 in human leukaemia. Finally, both proteins interact with the tumor suppressor pRb protein and subsequently can lead to regulation of the cell proliferation. The possible regulatory pathways that are controlled by c-Abl and D40 proteins are described here in details.