The scientists in the collaboration isolated UHRF1 from a functional genomics screen designed to identify genes that interfere with proliferation.
They found that UHRF1 expression is elevated in proliferating cells and primary tumors. The scientists further found that interference with UHRF1 ubiquitin ligase function rendered cells sensitive to the effects of chemotherapeutics.
Early cellular events associated with the creation of tumors often include loss of cell cycle checkpoints or alteration in growth signaling pathways. Identification of novel genes involved in cellular proliferation may lead to new classes of cancer therapeutics.
“We are particularly interested in the selective inhibition of ubiquitin ligases, since it could lead to pharmaceutical product candidates with higher specificity and lower toxicity for cancer patients,” said Dr Donald Payan, executive vice president and chief scientific officer of Rigel.
The study is part of a collaboration between Rigel and Johnson & Johnson that began in December 1998. The purpose of the collaboration is to identify and validate novel drug targets that regulate the cell cycle, which controls cancer progression.
Johnson & Johnson is currently moving forward targets identified in the collaboration to discover and develop drug candidates, which inhibit tumor cell growth or sensitize tumor cells to chemotherapeutic agents.