Ricerc@Sapienza

KDM5B / JARID1B is a histone demethylase involved in development and differentiation processes, in DNA damage repair, in gene expression regulation, in cancerogenesis and drug resistance. Although KDM5B is up regulated in many types of cancer, it may have a different function in luminal and basal breast cancers. Until now remains unclear what contextual determinants dictate whether KDM5B protein function as oncogene or tumor suppressor. Recently it has been proposed that the relative abundance of different KDM5B isoforms may contribute to tumor progression in melanoma, but the significance of the alternative transcripts of PLU-1 remains unclear. In this regard, a predicted protein isoform X1, never validated until now, is of particular interest. In fact, this expected isoform, lacking an N-terminal portion, may act as a negative dominant, maintaining the ability to bind chromatin and coregulators but losing its catalytic demethylase function. At the same time, it is possible that this isoform may also become a gain of function, since it includes an alternative exon that is not present in the canonical protein isoform, by giving the protein the ability to bind new interactors. Therefore, the understanding of the biological contribution of this and other protein predicted isoforms for tumor progression and chemoresistance in breast cancer and melanoma may be of crucial importance.