Entry into mitosis is essentially driven by cyclin B1, which is located in the
cytoplasm throughout interphase, but accumulates in the nucleus just before
mitosis occurs. Nuclear interaction partner of ALK (NIPA) plays a critical role
in cyclin B1 regulation. NIPA is normally phosphorylated during G2 and M
phases, resulting in an accumulation of cyclin B1. When NIPA sheds its
attached phosphate, it binds to SCF to form the SCFNIPA complex, a member
of the E3 ubiquitin ligases, which ubiquitinates cyclin B1, thereby targeting it
to the proteosome for degradation. Therefore, the accumulation of cyclin B1
is due to the inability of phosphorylated NIPA to bind to the molecule SCF,
thereby preventing the degradation of cyclin B1. An absence of NIPA causes
cyclin B1 to accumulate abnormally, leading to premature mitotic entry, loss
of checkpoint control and genomic instability, which are all associated with
cancer. The phosphorylated form of NIPA may also be involved in apoptotic
signaling pathways.