TGF-beta 1 inhibition of c-myc transcription and growth in keratinocytes is abrogated by viral transforming proteins with pRB binding domains.

Pietenpol JA, Stein RW, Moran E, Yaciuk P, Schlegel R, Lyons RM, Pittelkow MR, M√ľnger K, Howley PM, Moses HL
Cell. 1990 61 (5): 777-85

PMID: 2140528 · DOI:10.1016/0092-8674(90)90188-k

TGF-beta 1 is demonstrated to inhibit skin keratinocyte proliferation when added during the G1 phase of the cell cycle. Human foreskin keratinocytes transformed with either HPV-16 or -18 or SV40, however, were resistant to the growth inhibitory effects of TGF-beta 1. Since TGF-beta 1 appears to inhibit keratinocyte growth through down-regulation of c-myc, it was hypothesized that these DNA tumor viruses might be modulating the response to TGF-beta 1 via this pathway. Transient expression of proteins HPV-16 E7, adenovirus type 5 E1A, and SV40 large T antigen is demonstrated to block TGF-beta 1 suppression of c-myc transcription. This effect was not observed with DNA tumor virus transforming proteins mutated in their pRB binding domain. These observations indicate that pRB or another protein that interacts with this binding domain mediates TGF-beta 1 regulation of c-myc gene expression and growth inhibition.

MeSH Terms (19)

Adenovirus Early Proteins Amino Acid Sequence Animals Antigens, Polyomavirus Transforming Cells, Cultured Cell Transformation, Viral DNA-Binding Proteins Gene Expression Regulation Keratinocytes Molecular Sequence Data Oncogene Proteins, Viral Phosphoproteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-myc Recombinant Proteins Retinoblastoma Protein Transcription, Genetic Transfection Transforming Growth Factors

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