|Cell in prometaphase|
by Roy van Heesbeen
Previous to this report, Greatwall was shown to regulate cell division in invertebrates such as the Drosophilla melanogaster fly and its biochemistry has been characterized in Xenopus. The current work describes the generation of the first mammalian genetic model of this protein using mice. The authors found that cells lacking Greatwall are not capable of adequately dividing themselves even though they enter mitosis with normal kinetics. The deviation from normal cell division occurs after the nuclear envelope breaks down exposing nuclear components such as chromosomes to the cytoplasm and the enzyme activities localized there. Without Greatwall the DNA does not condense to form the correct structures and cell division is halted at prometaphase.
The potential therapeutic capacity of Greatwall is enhanced because it acts by blocking the function of PP2A, a frequently altered tumor suppressor. Therefore, inhibition of Greatwall could slow down cell division and reactivate a tumor suppressor that has been shown to be capable of inhibiting many oncogenic pathways involved in the development of cancer. The search now begins for compounds capable of inhibiting Greatwall and understanding which types of cancer would most benefit from treatment with a Greatwall inhibitor.
The title of the PNAS article is: 'Greatwall is essential to prevent mitotic collapse after nuclear envelope breakdown in mammals'