The present study using genetic approaches provide for the first time evidences that in contrast to its pivotal role in pathological angiogenesis. This clearly demonstrates that distinct molecular pathways govern angiogenesis and lymphangiogenesis and that PAI-1 plays distinct roles in the remodelling of both circulation systems in pathological conditions. Providing that PAI-1 antagonists are used to inhibit angiogenesis, our results reveal that this approach will not have any effect on lymphangiogenesis. Although PAI-1 is dispensable for lymphangiogenesis, it is worth noting that other proteolytic systems are mandatory for this process and particularly matrix metalloproteases such as the MMP-2 whose deficiency impairs lymphangiogenesis in in vitro and in vivo models. Cyclin-dependent kinasesare poised to play a central role in the orderly transition of the eukaryotic cells through different stages of the mitotic cell division cycle. The activities of the CDKs are controlled by a tight network of regulatory mechanisms, which comprise activatory/inhibitory phosphorylation and dephosphorylation events, controlled degradation of the cyclin partner and association with effectors. Several CDKIsfunction as tumour supressorsand loss/subversion of its activitiesresults in the development of tumours, cancers and neoplasms. The importance of CDKIs in benign and malignant leukaemias, urological and other diseases is a subject of intense ongoing investigation. Though initially considered as tumour suppressors based on their ability to block cell proliferation, CDKIs play pertinent roles in the regulation of a myriad of cellular processes including transcription, apoptosis, cell migration and cytoskeletal dynamics, which may be oncogenic under certain circumstances. Due to the involvement of CDKs in critical cellular roles, inhibition of CDKs harbors immense relevance for anticancer therapy. Inhibition of CDKs could be accomplished both by over expression of cellular CDKIsas well as pharmacological inhibitors. Cellular CDKIs e.g. the tumour suppressor gene products p16INK4, p21WAF1, and p27KIP1, form the starting point for the design of mechanism-based CDK inhibitors. Analysis of the structural aspects of cellular CDKIs leads to the identification of inhibitory lead peptides amenable to peptidomimetic development. Conversion of these peptides into pharmaceutically useful molecules provides a wealth of potential drug candidates capable of inhibiting CDKs, blocking cell-cycle progression, modulating transcription and inducing apoptosis selectively in cancer cells. Some of these, such as flavopiridol, LDN-193189 7-hydroxystaurosporineand roscovitine, have already reached the stage of ABT-199 clinical evaluation. These pharmacological CDKIs herald the opening of new avenues of clinical therapies against such intractable pathogens like human immunodeficiency virus and several protozoan parasites like Plasmodium, Trypanosoma and Leishmania. CDKIs also constitute potential targets for therapeutic stem cell manipulations. In the light of well established significance of CDKI proteins within the cell and in the development of pharmacological CDK inhibitors, it becomes essential to have facile methods of identifying these proteins. However, these exhibit a lot of diversity in their amino acid sequences. These are represented by INK4and Cip/Kipfamilies in mammals, Sic1 proteinin fungi and SIAMESE family and ICK/KRP family in plants. Owing to this enormous diversity, its identification is precluded by simple similarity-based approaches. As an alternative to similarity based methods, we applied two machine learning techniques.