Structural Mapping of the C-terminal Domain of Human P73

Abstract

Human P37 is a recently-discovered homologue of the yumor suppressor P73. The location of its gene in chromosome 1 is deleted in many cancers, including colon and breast cancers, melanoma and neuroblastoma. 1 Its gene encodes two splice-variants, P73 - α and β, both exhibiting high sequence and structural similarity to P53, with an N - terminal transactivation domain, a central DNA-binding domain, and an oligomerization domain. 1 However P73 - α contains 136 extra residues in its C - terminus compared to the β variant, and 213 additional residues when compared to P53. since this domain is not present in P53 or the P73β variant, it may be important in defining a unique function for P73, or may function in modulating P53 - like functions of P73 through alternative oligomerization arrangements or interactions. Toward understanding the functional and/or structural role of this C - domain of P73α, we have begun NMR spectroscopic studies of several construct of the C - terminus, chosen using sequence alignments with two other proteins which also exhibit an extended C - terminus: rat KET protein, 2 and squid(Loligo forbesi) P53. 1,2 We report here the NMR characterization of several constructs of C – terminus of P73 and the identification of a small folded globular domain formed by residues 487 – 554.