Phosphorylation of MCPH1 isoforms during mitosis followed by isoform‐specific degradation by APC/C‐CDH1

What is it about?

Microcephalin-1 (MCPH1) is a protein that helps control brain development and also helps to prevent cancer (it is a 'tumour suppressor protein'). As part of brain development, rapid cell growth occurs using a tightly controlled process called the cell cycle. This involves producing an exact copy of our genetic material/DNA (chromosomes) in a process called DNA replication, before dividing this equally between two new 'daughter' cells. Cell division is an essential part of growth/development and also ensures that damaged or dead cells can be replaced. The accurate division and separation of our chromosomes takes place during a process called mitosis and this is controlled by complex mechanisms, involving hundreds of cellular proteins. The activity of each of these proteins needs to be precisely ordered to make sure that no mistakes occur during mitosis. Microcephalin-1 (MCPH1) controls key events in mitosis and cells with defective MCPH1 show abnormal brain development due to mistakes in mitosis. MCPH1 is also a tumour suppressor protein - it has roles in repairing damage to our DNA, helping to prevent the mutations that can cause cancer. Despite these important roles, there is little known about the mechanisms that control the function of MCPH1. Given the cellular roles of MCPH1, such information will help us understand the mechanisms that control brain development and tumour suppression. We identify multiple new mechanisms that help to regulate the cellular function of MCPH1.

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