The Capicua (Cic) protein is an evolutionarily conserved nuclear factor with important roles in human biology. It acts, for example, by restricting the activity of genes involved in cell proliferation and, consequently, the loss of Cic function by mutation can lead to uncontrolled cell division and cancer. Moreover, one key feature of Cic is that it is sensitive and can be turned off by a major cell-to-cell communication system (the so-called Ras-MAPK signaling pathway) which is itself frequently mutated in human tumors.
Previously, we and others have discovered and characterized Cic function using the fruit fly Drosophila as a model. And further studies in mammals have confirmed a similar activity of Cic in these organisms. However, these analyses had not addressed the fact that Cic actually exists as two variants of different lengths and potentially exerting different activities. In fact, while most of what we know about Cic comes from studies on the shorter form (Cic-S), the function of the longer variant (Cic- L) has been a mystery for years.
Now, we have studied Cic-L in Drosophila and shown that it performs two different roles: a canonical function equivalent to that of Cic-S, and a novel, non-canonical function controlling the size and behavior of cells required for oocyte maturation. This second function, which affects the activity of conserved regulators of cell growth, is mainly mediated by a protein fragment of Cic-L that is not present in Cic-S, and is therefore very different in nature from the classical function of Cic. Since the structure of Cic-L is so well conserved in evolution, we have proposed that it also has dual roles in human development and disease.