Table 2.
Proteins involved in centriole number control, their functions and links to disease
| Gene symbol | Function | Links with disease |
|---|---|---|
|
| ||
| Centriole genes linked with tumorigenesis | ||
|
| ||
| PLK4 | Centriole duplication | Overexpressed in breast cancer. Controls invasion through regulation of the actin cytoskeleton. PLK4+/− mice are predisposed to liver and lung cancer |
| STIL | Centriole duplication | Promoter fused to TAL1 in T-Cell acute lymphoblastic leukaemia |
| NLP | Microtubule nucleation | Overexpressed in multiple cancers |
|
| ||
| Genes linked to MCPH | ||
|
| ||
| PLK4 | Centriole duplication | Mutations reduce the levels of PLK4 |
| STIL | Centriole duplication | Mutations inhibit the cell-cycle controlled degradation of STIL |
| CPAP | Controls centriole length and centriole duplication | Mutations weaken binding of CPAP to STIL |
| CEP135 | Centriole duplication | |
| CEP152 | Centriole duplication | |
| CEP63 | Centriole duplication | |
| CDK5RAP2/CEP215 | Centriole duplication | |
| WDR62 | Spindle pole organization; Centriole duplication | |
| ASPM | Spindle pole organization; Centriole duplication | |
| TUBGCP6 | Centriole duplication, component of the γTubulin ring complex | |
| TUBGCP4 | Component of the γTubulin ring complex | |
| CDK6 | Centrosome associated in mitosis | Mutations mislocalize CDK6 |
|
| ||
| Centriole genes linked to primordial dwarfism | ||
|
| ||
| PLK4 | Centriole duplication | Mutations reduce the levels of PLK4 |
| CPAP | Centriole duplication | |
| CEP152 | Centriole duplication | |
| CEP63 | Centriole duplication | |
| PCNT | Component of the PCM | Mutations mislocalize PCNT |
|
| ||
| Centriole genes linked with other disorders | ||
|
| ||
| ALMS1 | Functions in ciliogenesis | Alstrom Syndrome results in retinitis pigmentosa, deafness, obesity and diabetes. |
| OFD1 | Controls centriole length | Orofaciodigital syndrome results in malformations of the face, oral cavity and digits |
| C2CD3 | Controls centriole length | Orofaciodigital syndrome results in malformations of the face, oral cavity and digits |
Footnotes: Plk4 = Polo-like kinase 4; STIL = SCL/TAL1 Interrupting Locus; NLP = Ninein-Like Protein; CPAP = Centrosomal P4.1-Associated Protein; CEP135= Centrosomal Protein 135; CEP152 = Centrosomal Protein 152; CEP63 = Centrosomal Protein 63; CDK5RAP2/CEP216 = CDK5 Regulatory Subunit Associated Protein 2/Centrosomal Protein 216; WDR62 = WD Repeat Domain 62; ASPM = Abnormal Spindle Microtubule Assembly; TUBGCP6 = Tubulin Gamma Complex Associated Protein 6; TUBGCP4= Tubulin Gamma Complex Associated Protein 4; CDK6 = Cyclin Dependent Kinase 6; PCNT = Pericentrin/Kendrin; ALSM1= Alstrom Syndrome Protein 1; OFD1= Oral-Facial-Digital Syndrome 1; C2D3 = C2 Calcium Dependent Domain Containing 3; TAL1 = T-Cell Acute Lymphocytic Leukemia 1; PCM = Pericentriolar Material. MCPH = Autosomal recessive primary microcephaly.