D-type Cyclins and Cancer

This volume provides an integrated account of our current understanding of the functions of D-type cyclins during development and tumorigenesis, with special emphasis on the kinase-independent functions of these proteins. The volume will provide a thorough review of the latest discoveries on the new functions and interacting partners of mammalian cyclin Ds is crucial to explain their oncogenic and differentiation properties in different cellular contexts. The volume begins with a historical perspective of how D-type cyclins were first discovered and eventually cloned from cancer tissues, followed by an account on the canonical functions of cyclin Ds during the G1-S transition of the cell cycle. Several chapters will be devoted to review the functions of different D-type cyclins as transcriptional regulators and the mechanisms through which these novel functions could impact the tumorigenic process. Also discussed are emerging evidence has also pointed to a role of D-type cyclins, particularly cyclin D1, as a cytoplasmic regulator of various functions, a property that, in human cells at least, seem to be traceable to certain splice isoforms. In addition, chapters of the book will be devoted to discuss the oncogenic implications of the cytoplasmic variants of cyclin D1. Finally, a special chapter will be devoted to recent efforts to revise the canonical view of the "retinoblastoma pathway" to incorporate new evidence that suggests that cyclin D1's role in G1 is to singly-phosphorylate the retinoblastoma protein (pRb) for discrimination of target protein interactions. This work represents a significant departure from the view of cyclin D1 as a negative regulator of pRb and may have significant implications for the function of anti-neoplastic agents that target the cyclin D1-associated kinases.