| CENPJ (Centromere Protein J) | |
|---|---|
| Gene | [CENPJ](/genes/CENPJ) |
| UniProt | Q9Y3D9 |
| PDB Structures | 4NTG, 4UTH |
| Molecular Weight | 136 kDa |
| Localization | Centrosome, centrioles |
| Protein Family | PLK4 family (related) |
CENPJ (Centromere Protein J), also known as CPAP (Centromere Protein N), is a crucial centrosomal protein essential for centriole duplication, centrosome maturation, and proper mitotic spindle formation. It plays a fundamental role in neurogenesis, and mutations in the CENPJ gene cause autosomal recessive primary microcephaly (MCPH6), Seckel syndrome, and Meier-Gorlin syndrome [1]. This protein is particularly important during brain development, where proper centrosome function is critical for neural progenitor cell division and cortical expansion.
CENPJ is a 136 kDa protein encoded by the CENPJ gene (also known as CPAP), located on chromosome 13q12.2. It is a member of the PLK4 family of serine/threonine kinases, though CENPJ itself lacks kinase activity and functions as a scaffolding protein [2]. The protein localizes to the centrosome, specifically at the centrioles, where it serves as a molecular platform for recruiting other proteins necessary for centriole duplication and centrosome function.
During cell division, CENPJ ensures proper chromosome segregation by facilitating spindle assembly through its role at the centrosome. In neural progenitor cells, CENPJ is critical for maintaining the balance between symmetric and asymmetric cell divisions that drive cortical growth [3].
CENPJ has several specialized structural domains that mediate its diverse functions:
The protein adopts an elongated conformation that allows it to span across the centriolar structure, positioning its interaction domains strategically for recruiting duplication machinery components [4].
Within the centrosome, CENPJ performs several essential cellular functions:
CENPJ is the master regulator of centriole duplication, initiating new centriole formation by forming a complex with STIL (SIL) and PLK4 [2:1]. This complex recruits SAS-6, which nucleates the central tube of the new centriole. CENPJ maintains strict control over centriole copy number, ensuring each daughter cell inherits exactly one pair of centrioles.
During mitosis, CENPJ helps recruit pericentriolar material (PCM) proteins to the centrosome, enabling centrosome maturation and proper spindle pole formation [5].
CENPJ ensures proper mitotic spindle assembly by coordinating centrosome function with microtubule nucleation, critical for accurate chromosome segregation.
In developing neural progenitor cells, CENPJ regulates mitotic spindle orientation through its interaction with apical polarity complexes [6]. This orientation determines whether neural progenitors undergo symmetric (expansive) or asymmetric (differentiation) divisions, directly impacting cortical size.
CENPJ mutations cause autosomal recessive primary microcephaly type 6 (MCPH6), characterized by:
The pathogenic mechanism involves defective neural progenitor cell division due to centrosomal dysfunction, leading to premature neuronal differentiation and reduced neuronal pool size [3:1].
CENPJ mutations cause Seckel syndrome type 2, which represents part of the spectrum of disorders related to MCPH:
CENPJ expression is altered in various cancers:
CENPJ represents a potential therapeutic target in several contexts:
Bond J, et al. Identification of the gene mutated in primary microcephaly. 2005. ↩︎
Inserna G, et al. CENPJ mutations and neural progenitor cell cycle regulation. 2020. ↩︎ ↩︎
Chen JF, et al. CENPJ regulates mitotic spindle orientation in neural progenitors. 2017. ↩︎