Hairless is translocated to the nucleus via a novel bipartite nuclear localization signal and is associated with the nuclear matrix

Hair follicle cycling is an exquisitely regulated and dynamic process consi sting of phases of growth, regression and quiescence. The transitions betwe en the phases are governed by a growing number of regulatory proteins, incl uding transcription factors. The hairless (hr) gene encodes a putative tran scription factor that is highly expressed in the skin, where it appears to be an essential regulator during the regression of the catagen hair follicl e, In hairless mice, as well as humans with congenital atrichia, the absenc e of hr gene function initiates a premature and abnormal catagen due to a d ysregulation of apoptosis and cell adhesion, and defects in the signaling r equired for hair follicle remodeling. Here, we report structure-function st udies of the hairless gene product, in which we identify a novel bipartite nuclear localization signal (NLS) of the form KRA(X13) PKR, Deletion analys is of the mouse hr gene mapped the NLS to amino acid residues 409-427, Indi rect immunofluorescence microscopy of cells transiently transfected with ha irless-green fluorescent fusion proteins demonstrated that these amino acid residues are necessary and sufficient for nuclear localization. Furthermor e, nuclear fractionation analysis revealed that the hr protein is associate d with components of the nuclear matrix.