Alternative titles; symbols
HGNC Approved Gene Symbol: CENPI
Cytogenetic location: Xq22.1 Genomic coordinates (GRCh38): X:101,098,204-101,181,859 (from NCBI)
By database searching with a sequence identified near the DRP2 gene (300052) on chromosome Xq22, Roberts et al. (1996) found that the sequence showed similarity to the rat LRPR1 gene. The deduced 756-amino acid human protein shares 72% sequence identity with the rat protein.
Slegtenhorst-Eegdeman et al. (1995) found that the LRPR1 gene was rapidly transcriptionally activated in response to follicle-stimulating hormone (FSH; 136530) stimulation of rat testicular Sertoli cells, both in vitro and in vivo. The response of LRPR1 was specific to FSH; it was refractory to activation by a wide range of other hormones and growth factors. FSH, a gonadotropic hormone secreted by both the male and the female mammalian anterior pituitary gland, is responsible, with luteinizing hormone (152780), for the regulation of follicular maturation and ovulation in females. Roberts et al. (1996) hypothesized that the specificity of the response of LRPR1 to FSH makes LRPR1 a potential candidate for human X-linked disorders of gonadal development.
Liu et al. (2003) examined the fate of HeLa cells whose kinetochores were depleted of CENPI by antibody injection. Cell cycle progression was significantly delayed following CENPI depletion, there was a high incidence of mitotic cells containing monopolar chromosomes because only 1 of the sister kinetochore pair was attached to the pole, and there was a defect in mitotic checkpoint. Cells with misaligned chromosomes did not arrest in mitosis but divided to produce cells with micronuclei and abnormally shaped nuclei. A similar phenotype was observed when interfering RNA was used to block expression of CENPI. Liu et al. (2003) determined that the localization of MAD2 (601467) and CENPF (600236) to kinetochores was sensitive to the loss of CENPI, and that localization of MAD1 (602686) to kinetochores was dependent on CENPI. The transient delay in mitosis was MAD2 dependent, even though the kinetochores were depleted of MAD2. The delay in mitosis was extended when the number of unattached kinetochores was increased, suggesting that the collective output from many unattached kinetochores is required to reach a threshold signal of 'wait for anaphase' to sustain a prolonged mitotic arrest.
Roberts et al. (1996) identified the LRPR1 gene on chromosome Xq22. They found by hybridization to YACs and to cosmids isolated from that region that LRPR1 is transcribed in a proximal-to-distal direction and lies approximately 40 kb proximal to DRP2, while BTK (300300), the gene that is mutant in X-linked agammaglobulinemia (300755), lies approximately 300 kb distal.
Liu, S.-T., Hittle, J. C., Jablonski, S. A., Campbell, M. S., Yoda, K., Yen, T. J. Human CENP-I specifies localization of CENP-F, MAD1 and MAD2 to kinetochores and is essential for mitosis. Nature Cell Biol. 4: 341-345, 2003.
Roberts, R. G., Kendall, E., Vetrie, D., Bobrow, M. Sequence and chromosomal location of a human homologue of LRPR1, an FSH primary response gene. Genomics 37: 122-124, 1996. [PubMed: 8921378] [Full Text: https://doi.org/10.1006/geno.1996.0528]
Slegtenhorst-Eegdeman, K. E., Post, M., Baarends, W. M., Themmen, A. P. N., Grootegoed, J. A. Regulation of gene expression in Sertoli cells by follicle-stimulating hormone (FSH): cloning and characterization of LRPR1, a primary response gene encoding a leucine-rich protein. Molec. Cell. Endocr. 108: 115-124, 1995. [PubMed: 7758824] [Full Text: https://doi.org/10.1016/0303-7207(94)03468-9]