Human PRDM2: Structure, function and pathophysiology

• Published in: Biochimica et biophysica acta. Gene regulatory mechanisms Vol. 1861; no. 7; pp. 657 - 671
• Main Authors: Sorrentino, A., Rienzo, M., Ciccodicola, A., Casamassimi, A., Abbondanza, C.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-07-2018
• Subjects: Cancer; Estradiol; Gene products; Human diseases; Molecular function; PRDM2/RIZ; Human diseases; Gene products; PRDM2/RIZ; Molecular function; Estradiol; Cancer
• ISSN: 1874-9399; 1876-4320
• DOI: 10.1016/j.bbagrm.2018.06.002

PRDM2/RIZ is a member of a superfamily of histone/protein methyltransferases (PRDMs), which are characterized by the conserved N-terminal PR domain, with methyltransferase activity and zinc finger arrays at the C-terminus. Similar to other family members, two main protein types, known as RIZ1 and RIZ2, are produced from the PRDM2 locus differing by the presence or absence of the PR domain. The imbalance in their respective amounts may be an important cause of malignancy, with the PR-positive isoform commonly lost or downregulated and the PR-negative isoform always being present at higher levels in cancer cells. Interestingly, the RIZ1 isoform also represents an important target of estradiol action downstream of the interaction with hormone receptor. Furthermore, the imbalance between the two products could also be a molecular basis for other human diseases. Thus, understanding the molecular mechanisms underlying PRDM2 function could be useful in the pathophysiological context, with a potential to exploit this information in clinical practice.
•PRDM2/RIZ belongs to a histone methyltransferase family containing Zn-finger motifs.•RIZ1, but not RIZ2, contains the PR domain, which confers methyltransferase activity.•Imbalance in the RIZ1/RIZ2 amounts may represent an important cause of malignancy.•A PRDM2 frameshift mutation affecting the (A)9 repeat is a cancer driver mutation.•RIZ1 is a target of estradiol action through interaction with hormone receptor.