Ski interacting protein (Skip) plays an important role in the transforming activity of both v-Ski and EBNA2 (Epstein-Barr virus encoded latency protein) and is involved in EBNA2 and NotchIC activation of CBF1-repressed promoters. We have previously shown that Skip acts as a transcriptional co-activator on a number of cellular and viral promoters. Here, we report that Skip also interacts with pRb and, in cooperation with Ski, can overcome pRb-induced transcriptional repression. We show a strong and direct interaction between pRb and Skip, and we map the site of interaction to amino acid residues 171-353 of the evolutionarily conserved SNW domain of Skip. Furthermore, the combination of Skip and Ski can successfully overcome the G1 arrest and flat cell phenotype induced by pRb. Taken together, these studies suggest that one potential function of the Skip-Ski complex is to overcome the growth-suppressive activities of pRb.

E7 is the major transforming protein of human papillomavirus (HPV), which is implicated in the development of cervical cancer. The transforming activity of E7 has been attributed in part to its interaction with the retinoblastoma (Rb) tumour suppressor; however, the Rb interaction alone is not su cient for transformation by E7. In a screen for cellular targets of HPV E7, we identi®ed the Ski interacting protein, Skip, as a new interacting partner of E7. We show that HPV-16 E7 associates with Skip via sequences in its carboxy terminal region, and the evolutionarily conserved proline rich sequences (PRS) of the SNW domain of Skip. E7 functionally targets Skip in vivo and inhibits its transcriptional activation activity. Two transformation defective mutants of E7 were identi®ed that failed both to bind Skip and to inhibit its transcriptional activity. These results suggest that inhibition of Skip function may contribute to cell transformation by HPV-16 E7. Oncogene (2001) 20, 7677 ± 7685.

Ski interacting protein (Skip) has been found to bind to the highly conserved region of Ski, which is required for its transforming activity. Ski is a unique oncoprotein that is involved in inducing both transformation and differentiation. At the molecular level, Ski has been shown to exhibit either co-activator or co-repressor activity depending on the cellular and promoter context. We were interested in further elucidating the biological implications of the Ski-Skip interaction. Here we have identified the SNW domain of Skip as the interaction region for Ski. This domain of Skip is highly conserved in all the Skip homologues identified from different species. Using a series of reporter plasmids, we show that Skip is a potent transcriptional activator of many different promoters, the activity of which was also mapped to the conserved core SNW domain of the protein. Addition of excess Ski further augmented the transcriptional activities of Skip, suggesting that one of the ways in which Ski brings about transformation is by binding and cooperating with the SNW domain of Skip in transcriptional activation.

Vaccination is the only pragmatic approach to control foot and mouth disease in India. Strict quality control measures are essential to supply potent vaccine to the field application, in addition to monitoring the performance of the vaccine in the field. During the process of monitoring, an outbreak of FMD in vaccinated animals caused by type "O" virus in Tanjavur district of Tamil Nadu and a type "O" virus from unvaccinated herd of Karnataka were studied. Field isolates and vaccine virus were sequenced and analyzed. Data indicated that the virus from the outbreak in vaccinated cattle was a variant which could escape neutralization by antibodies against vaccine virus.

The antigenic variation in Foot and Mouth Disease Virus (FMDV) is very high. The effective strategy to control the Foot and Mouth Disease (FMD) in India which is a habitat of four serotypes O, A, C and Asia 1, is by regular vaccination, using the vaccine strain most suitable for the local situation. India is an endemic country with the disease being widely distributed. Selection of vaccine strain should therefore need the information on the circulating viruses. Asia 1 causes the second largest number of disease outbreaks in India. As there is no information available with respect to the extent of antigenic variation in FMDV type Asia 1, we have studied FMDV isolates from vaccinated and unvaccinated animals from different parts of the country and compared their relationship with Asia 1 vaccine virus. The immunogenic, hypervariable region of viral protein 1 (VP1) gene was amplified by RT-PCR and sequenced. Analysis of sequence data showed that the viruses from two field outbreaks of Southern India were closely related to each other when compared to the isolate from the North and all the three isolates are away from the vaccine virus.