CENPE

Description

The CENPE (centromere protein E) is a protein-coding gene located on chromosome 4.

Centromere-associated protein E (CENPE) is a kinesin-like motor protein encoded by the CENPE gene in humans. It accumulates during the G2 phase of the cell cycle, appearing at the centromere region of chromosomes during prometaphase. Unlike other centromere-associated proteins, it is absent during interphase. CENPE is thought to be involved in mammalian chromosome movement and/or spindle elongation, also known as Kinesin-7. Mutations in CENPE lead to autosomal recessive primary microcephaly type 13, which includes skeletal abnormalities and immunodeficiency.

CENPE is a microtubule plus-end-directed kinetochore motor that plays a critical role in chromosome congression, microtubule-kinetochore attachment, and spindle assembly checkpoint activation. It drives chromosome congression by facilitating the lateral sliding of polar chromosomes along spindle microtubules towards the spindle equator and by aiding the formation and maintenance of connections between kinetochores and spindle microtubules. CENPE preferentially transports pole-proximal chromosomes towards the spindle equator along detyrosinated microtubule tracks. Acting as a processive bi-directional tracker of dynamic microtubule tips, CENPE continues to be active at kinetochores after chromosome congression, strengthening their links with dynamic microtubule ends. In cells depleted of NDC80, CENPE suppresses chromosome congression, contributing positively to congression only when microtubules are stabilized. CENPE is essential for establishing stable attachments between kinetochores and spindle microtubules, which involves its recruitment of other proteins like BUB1B, MAD1, and MAD2 to the kinetochore. CENPE contributes to spindle assembly checkpoint activation (SAC) by interacting with BUB1B, activating its kinase activity, which is crucial for SAC activation. CENPE is essential for the mitotic checkpoint signal at individual kinetochores, preventing aneuploidy due to single chromosome loss.

CENPE is also known as CENP-E, KIF10, MCPH13, PPP1R61.

Associated Diseases

• Seckel syndrome
• Microcephaly 13, primary, autosomal recessive
• Autosomal recessive primary microcephaly