B23 Inhibits Eg5-mediated Microtubules Depolymerization Via Inactivating Its Atpase Activity

Nucleophosmin/B23, an abundant nucleolar protein, plays multiple roles in cell growth and proliferation. There are two B23 isoforms. Subtype 1, which is the full length of B23, is 35 amino acids longer than Subtype 2. C-terminus of B23 ,which is called DNA and RNA Binding Domain (DRBD), is tend to mutanted., and its mutations could induce Acute myeloid leukemia (AML). It is reported that B23 mutations lead to aberrant localization of the B23 protein into the cytoplasm and promote AML occurrence. Despite its functions inside the nucleus is well-studied, functions of B23 in the cytoplasm remains elusive. Therefore, it is unclear exactly that how B23 mutations lead to AML. We then tried to find the meaning of B23 locates in the cytosol.Firstly, a Yeast-Two-hybrid system was used to screen B23 novel interact partners. And a member of the kinesin family, Eg5, was found and identified to interact with B23. It is further proved that B23 directly interacts with Eg5 in the cytosol. This evidences give some indications about the function of B23 in cytoplasm.An interesting result was then found that in opposite to Eg5, B23 promotes microtubule (MT) polymerization. This was the first evidence that B23 plays an important role in regulating MT dynamics in cytoplasm.Further results showed that B23 regulates MT dynamics by directly inhibiting Eg5 ATPase activity. It makes senses for studying novel B23 functions. Furthermore, as Eg5 is an important anti-neoplasmic drug target, and wild type B23 could inhibit AML development, whether the inhibitors of Eg5 such as mimics of DRBD of B23 could be used in treating AML patients is of clinical interest.In a word, our works suggest that B23 has an important function in cytoplasm.