Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.22 (cdc2)
 8,319 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The progression of mammalian gametogenesis requires a precise balance between cell-cycle activities and elimination of defective gametogenic cells to ensure the perpetuation of species. Both spermatogonia and oogonia are stem cell populations committed to meiosis with the aim of generating haploid gametes for fertilization. At puberty, mitotically dividing spermatogonial cell cohorts maintain the ability of cell renewal and occupy niches in the seminiferous tubule. In contrast, mitotically dividing oogonial cell cohorts produced in the fetal ovary, are exclusively committed to meiosis and produce primordial follicles housing a primary oocyte surrounded by somatic follicular cells. A consistent physiological event during mammalian gametogenesis is the disposal of spermatogenic cells by apoptosis and ovarian follicles by atresia. Cyclin-dependent kinases (Cdks) and their cyclin partners coordinate the activities of the cell cycle. An additional cell-cycle regulatory component is the centrosome. The centrosome harbors regulatory proteins controlling the normal progression of the cell cycle. Changes in individual centrosome proteins can lead to cell-cycle arrest and a decrease in the genomic protective function of p53 that promotes apoptosis. Disruption of cyclin A1, Cdk2, and Cdk4 expression in transgenic mice results in infertility and gonadal atrophy. Cdk-cyclin complexes interact with regulatory proteins, which may fine-tune the activities of the complex. One of the many regulatory proteins is p12, a 115 amino acid growth suppressor polypeptide designated p12(CDK2AP1), partner of Cdk2 and with binding affinity to DNA polymerase alpha/primase. Overexpression of p12 is associated with testicular and ovarian atrophy without affecting fertility. Ectopic expression of p12 was driven by the keratin 14 promoter. Keratin 14 is the pairing partner of keratin 5 and both keratins are expressed in testis. The efficiency of keratin promoters in driving ectopic gonadal gene expression, the association of gonadal atrophy with the ectopic expression of a Cdk2 regulatory protein and the centrosome, as a reservoir of cell-cycle regulatory proteins, open new experimental opportunities to address still lingering questions concerning cell differentiation and division during mammalian gametogenesis.
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PMID:Cell-cycle regulation and mammalian gametogenesis: a lesson from the unexpected. 1670 69

We report the extremely unusual occurrence of a cellular angiofibroma (CAF) with atypical (bizarre) cells in the spermatic cord. We present a 63-year-old man, who was referred to the Urology Service with a six-month history of a slowly growing painless nodule in the right inguino-scrotal area. The clinical impression was that of a lipoma. The mass was locally excised. Gross examination showed a well-circumscribed neoplasm attached to the spermatic cord and measuring 5cm in the greatest dimension. Microscopic examination of the tumor showed the appearance of CAF with scattered severely atypical (bizarre) cells distributed throughout the lesion. By immunohistochemistry, atypical cells showed diffuse expression of p16, CDK-4, CD34 and vimentin. Keratin AE1/AE3, S-100 protein, p53, and epithelial membrane antigen were negative. The patient is free of disease two months after tumor excision. To the best of our knowledge, this is the third case of CAF with atypical (bizarre) cells occurring in the paratesticular area. Pathologists should be aware of this morphological variation of CAF to avoid misdiagnosis and over-treatment.
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PMID:Paratesticular cellular angiofibroma with atypical (bizarre) cells: case report and literature review. 2358 66