| Title: |
Human T-cell leukemia virus type 1 Tax and cell progression. Role of cyclin D-cdk and p110 Rb |
| Authors: |
NEUVEUT C; LOW KG; MALDARELLI F; SCHMITT I; GRASSMANN R; JEANG KT; MAJONE, FRANCA |
| Contributors: |
Neuveut, C; Low, Kg; Maldarelli, F; Schmitt, I; Majone, Franca; Grassmann, R; Jeang, Kt |
| Publisher Information: |
American Society for Microbiology / DC:1752 N Street Northwest:Washington, DC 20036:(202)737-3600, EMAIL: jadelman@asmusa.org, INTERNET: http://www.asmusa.org/asm.htm, Fax: (202)942-9342 |
| Publication Year: |
1998 |
| Collection: |
Padua Research Archive (IRIS - Università degli Studi di Padova) |
| Subject Terms: |
RETINOBLASTOMA GENE-PRODUCT; DEPENDENT KINASE INHIBITORS; LONG TERMINAL REPEATS; HTLV-1 TAX |
| Description: |
Human T-cell leukemia virus type 1 is etiologically linked to the development of adult T-cell leukemia and various human neuropathies. The Tax protein of human T-cell leukemia virus type I has been implicated in cellular transformation. Like other oncoproteins, such as Myc, Jun, and Fos, Tax is a transcriptional activator. How it mechanistically dysregulates the cell cycle is unclear. Previously, it was suggested that Tax affects cell-phase transition by forming a direct protein-protein complex with p16(INK4a), thereby inactivating an inhibitor of G1-to-S-phase progression. Here we show that, in T cells deleted for p16(INK4a), Tax can compel an egress of cells from G0/G1 into S despite the absence of serum. We also show that in undifferentiated myocytes, expression of Tax represses cellular differentiation. In both settings, Tax expression was found to increase cyclin D-cdk activity and to enhance pRb phosphorylation. In T cells, a Tax-associated increase in steady-state E2F2 protein was also documented. In searching for a molecular explanation for these observations, we found that Tax forms a protein-protein complex with cyclin D3, whereas a point-mutated and transcriptionally inert Tax mutant failed to form such a complex. Interestingly, expression of wild-type Tax protein in cells was also correlated with the induction of a novel hyperphosphorylated cyclin D3 protein. Taken together, these findings suggest that Tax might directly influence cyclin D-cdk activity and function, perhaps by a route independent of cdk inhibitors such as p16(INK4a). |
| Document Type: |
article in journal/newspaper |
| File Description: |
STAMPA |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/9584203; info:eu-repo/semantics/altIdentifier/wos/WOS:000073628800053; volume:18; firstpage:3620; lastpage:3632; numberofpages:13; journal:MOLECULAR AND CELLULAR BIOLOGY; https://hdl.handle.net/11577/110128 |
| Availability: |
https://hdl.handle.net/11577/110128 |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Accesso gratuito |
| Accession Number: |
edsbas.E7B6CBA8 |
| Database: |
BASE |