Jabez Bok

Presented by Sidney Strickland on behalf of Robert G. Roeder

B.S., University of Wisconsin, Madison

Mechanism of Action of ING4 as a Transcriptional Coactivator of p53

Jabez Bok hails from Singapore, and after earning his undergraduate degree at the University of Wisconsin, he joined The Rockefeller University as part of the Singapore A*STAR program. With a longstanding interest in gene expression, Jabez joined my laboratory to learn and apply biochemical approaches to the regulation of transcription, the first step in gene expression, through chemical modifications of the histone proteins that package DNA. Notably, his focus was on histone acetylation, which was discovered here at Rockefeller in the 1960s by the late Vincent Alfrey and linked directly to transcriptional regulation through the pioneering studies of our colleague David Allis.

Relevant facts regarding histone acetylation are that there are many different modifications of the four core histones, that they are generally linked to transcriptional activation, and that they are deposited by a large number of distinct histone acetyltransferases that often occur in large multi-subunit complexes. Jabez chose to work on a particular complex, the ING4 complex, because it had been linked functionally to the action of the tumor suppressor protein p53, which is mutated in over half of human cancers, and because its mechanism of action was poorly understood and represented a challenging problem for an ambitious graduate student. After mastering critical biochemical techniques, including the assembly of recombinant chromatin templates and the purification and characterization of specific multi-protein complexes, Jabez proceeded to provide major new insights into p53 target gene activation through the ING4 complex. He showed, for example, that the ING4 “complex” actually consisted of two structurally distinct complexes with different histone acetylation specificities and that it acted in conjunction with both a different well-characterized histone acetyl-transferase (p300) and a distinct chemical modification (namely methylation) on histones. Thus, important new ING4 co-activator mechanisms for the tumor suppressor p53 were demonstrated, and have potential therapeutic implications.

With his persistent passion for a deeper understanding of the role of chromatin structure and function in gene regulation, admittedly one of the most topical areas in all of biology, Jabez has returned to A*STAR in Singapore for postdoctoral work in a prominent laboratory in this area. We are grateful for his stellar contributions to our laboratory and will remember his thoughtful and diligent attention to his studies, and especially his very gracious manner. We wish him the best of luck as he continues to explore fundamental aspects of gene regulation through chromatin modifications.