HSP70-2 heat-shock protein of mouse spermatogenic cells.
The HSP70 heat-shock proteins are molecular chaperones that assist other proteins in folding, transport, and assembly into complexes. The genes for these proteins are either constitutively expressed (Hsc70, Grp78), or their expression is induced by heat shock and other stresses (Hsp70-1, Hsp70-3). Two additional genes encode proteins that are developmentally regulated and expressed specifically in spermatogenic cells (Hsp70-2, Hsc70t). The HSP70-2 protein is synthesized during the meiotic phase of spermatogenesis and is abundant in pachytene spermatocytes. Studies in transgenic mice indicated that the region between nucleotides -640 and +1 contains promoter sequences necessary for expression of Hsp70-2 in spermatocytes. Because of the pattern of gene expression, it was hypothesized that HSP70-2 is a chaperone necessary for completion of meiosis in spermatogenic cells. The gene knockout approach was used to test this hypothesis, and it was found that male mice homozygous for the mutation were infertile, whereas homozygous females were fertile. Spermatogenesis was disrupted, with the nuclei of late pachytene spermatocytes often appearing fragmented and spermatids being absent. Disruption of spermatogenesis occurred at the G2-M phase transition in prophase of meiosis I, and all pachytene spermatocytes underwent apoptosis. It was demonstrated that HSP70-2 is a chaperone for Cdc2, with their association allowing Cdc2 to acquire the necessary conformation to form a heterodimer with cyclin B1, leading to changes in Cdc2 phosphorylation and the development of kinase activity necessary for the G2-M phase transition. This appears to be the first demonstration that interaction between an HSP70 protein and a cyclin-dependent kinase is necessary for progression of the cell cycle.
Gamete Biology Section, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
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D000818:Animals; D002453:Cell Cycle / Q000235:genetics* / Q000502:physiology; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005298:Fertility / Q000502:physiology; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013091:Spermatogenesis / Q000235:genetics* / Q000502:physiology
D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D018844:Cyclin-Dependent Kinases