TOX


Thymocyte selection-associated high mobility group box protein TOX is a protein that in humans is encoded by the TOX gene.

Structure and function

The TOX gene encodes a protein that belongs to a large superfamily of chromatin associated proteins that share an approximately 75 amino acid DNA binding motif, the HMG -box. Some high mobility group box proteins contain a single HMG box motif and bind DNA in a sequence-specific manner, while other members of this family have multiple HMG boxes and bind DNA in a sequence-independent but structure-dependent manner. While TOX has a single HMG-box motif, it is predicted to bind DNA in a sequence-independent manner. TOX is also a member of a small subfamily of proteins that share almost identical HMG-box sequences. TOX3 has been identified as a breast cancer susceptibility locus. TOX is highly expressed in the thymus, the site of development of T lymphocytes. Knockout mice that lack TOX have a severe defect in development of certain subsets of T lymphocytes.

Role in diseases

In cancer or during chronic viral infection, TOX is necessary for T cell persistence but also drives T-cell "exhaustion" thus contributing to diminished anti-tumor or anti-viral function in these cells.