Polo-like kinase (Plk) family of serine/threonine kinase play Key regulator for the mitotic progression in mammalian cells is the family known as polo-like kinases (Plks). Plk1 is the most well studied member of this family (see figure). Currently, we are studying the role and functional significance of Plk1 in melanoma development and progression. More specifically, in one of our ongoing project under this program, we are testing the hypothesis that Plk1 plays a critical role in melanoma via modulation of Notch signaling. In a recent study (J Invest Dermatol, 129: 2843-53, 2009), we have found that, i) Plk1 is over-expressed in both clinical tissue specimens and cultured human melanoma cells when compared to normal skin tissues and cultured normal melanocytes, respectively; and ii) genetic as well as chemical inhibition of Plk1 results in a decrease in growth/viability nd induces a mitotic catastrophe, G2/M phase arrest and apoptosis in multiple melanoma cells without affecting the normal human melanocytes. This study suggested that Plk1 may have an important role in melanoma survival and/or progression. As a follow-up of this study, we are currently assessing if Plk1 plays a critical role in Notch signaling and melanoma development and survival through regulatory phosphorylation of Numb, an antagonist of NICD (Notch intracellular domain). The outcome of this work may lead to development of novel strategies towards the management of melanoma.