Transforming growth factor beta down-regulation of CKShs1 transcripts in growth-inhibited epithelial cells.

CKShs1 is a mammalian homologue of the yeast suc1 and CKS1 genes, for which the null mutation leads to arrest in both the G1 and G2 phases of the cell cycle in Saccharomyces cerevisiae. Northern blot analysis revealed that transcript levels of CKShs1 are strongly down-regulated in mink lung cells and moderately down-regulated in BALB keratinocytes within 10 h of exposure to transforming growth factor beta (TGF-beta), whereas growth arrest of both cell lines requires at least 15 h of TGF-beta treatment. As a genetic test for the potential role of CKShs1 in TGF-beta growth regulation, we analyzed a stably transfected derivative of mink lung cells that constitutively overexpresses a truncated form of the type 2 TGF-beta receptor and is resistant to TGF-beta growth inhibition; CKShs1 transcripts are not down-regulated by TGF-beta in this mutant cell line. TGF-beta down-regulation of CKShs1 transcripts is specific, since mRNA levels of mammalian G1 cyclins D1, D2, and D3 do not change in response to TGF-beta in either cell line. Cyclin D1 and cyclin D2 transcripts are strongly induced by epidermal growth factor, and beta 2-microglobulin transcripts are strongly induced by TGF-beta in BALB keratinocytes released from quiescence by addition of epidermal growth factor. Our results suggest a role for CKShs1 gene products in TGF-beta growth arrest of epithelial cells.