On the Effects of Leukemogenic Nucleoporin Fusion Proteins on Nucleocytoplasmic Transport and Gene Expression

Abstract

Chromosomal translocations involving NUP98 and NUP214 genes are recurrently reported in hematologic neoplasms of aggressive nature. Such genomic aberrations encode fusion proteins that conserve the phenylalanine-glycine (FG) domain of the respective nucleoporin fused to a wide range of partners. A common feature of most leukemia patients expressing Nup98 or Nup214 fusion proteins is the upregulation of HOX clustered genes. Consequently, cells expressing Nup98 or Nup214 fusion proteins exhibit perturbed cellular functions that translate in increased self-renewal capacity and impaired cellular differentiation. Given the high affinity of both nucleoporins to several nuclear transport receptors (NTRs) and particularly to the protein export receptor CRM1, both Nup98 and Nup214 are key players in the process of nucleocytoplasmic transport of macromolecules across the nuclear pore complex. Besides their role in nuclear transport, Nup98 and Nup214 participate in a myriad of cellular processes, such as epigenetic memory, mitotic regulation, and gene expression. In this chapter, we summarize the current findings on the effects of Nup98 and Nup214 fusions on cell behavior and their role in the etiology of leukemia.