Proteins and compositions for modulating mitosis

Details Proteins and compositions for modulating mitosis Proteins and compositions for modulating mitosis

A - Human Necessities

61

K

A61K 38/08 (2006.01) A61K 38/17 (2006.01) C07H 21/04 (2006.01) C07K 7/00 (2006.01) C07K 14/435 (2006.01) C07K 14/47 (2006.01) C12N 5/10 (2006.01) C12N 15/12 (2006.01) C12N 15/70 (2006.01) C12N 15/74 (2006.01) C12N 15/79 (2006.01) C12N 15/85 (2006.01) C12P 21/02 (2006.01)

Patent

CA 2274734

The protein encoded by the human gene HEC(<u>h</u>ighly <u>e</u>xpressed in <u>c</u>ancer) contains a long series of leucine heptad repeats and appears to be crucial for normal mitosis. HEC localizes to the nuclei of interphase cells and redistributes to centromeres during M phase. Ectopic expression of a mutant HEC containing only the heptad repeats results in the inability of cells to divide more than once. Inactivation of HEC results in disordered sister chromatid alignment and separation, as well as in the formation of non viable cells with multiple, fragmented micronuclei. HEC interacts through its leucine heptad repeats with several proteins involved in mitosis, including nek2, sb1.8, and two different regulatory subunits of the 26S proteasome, MSS1 and p45. These biochemical properties of HEC suggest its potential roles in modulating proteins important for spindle attachment to kinetochores, sister chromatic movement, and M phase progression.

La protéine codée par le gène humain HEC ("fortement exprimé dans le cancer") contient une longue série de répétition heptadiques de leucine et semble être cruciale pour la mitose normale. Le gène HEC se localise sur les noyaux de cellules d'interphase et se redistribue sur des centromères pendant la phase M. L'expression ectopique d'un HEC mutant contenant les seules répétitions heptadiques a pour effet d'empêcher les cellules de se diviser plus d'un fois. Il résulte de l'inactivation de HEC un alignement et une séparation désordonnés des chromatides soeurs ainsi que la formation de cellules non viables contenant plusieurs micronoyaux fragmentés. HEC interagit pas ses répétitions heptadiques de leucine de leucine avec plusieurs protéines impliquées dans la mitose telles que nek2, sb1.8 et deux sous-unitésw de régulation différentes du protéasome 26S : MSS1 et p45. Ces propriétés biochimiques de HEC suggèrent ses rôles potentiels dans la modulation de protéines importantes pour la fixation de centromères sur de cinétochores, le mouvement de chromatine soeur et la progression en phase M.

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