P53 FAMILY MEMBERS AS TRANSCRIPTIONAL TARGETS OF DELTAEF1 REPRESSORS

Our studies aim to understand the molecular mechanisms underlying the differentiation and developmental processes. The comprehension and the acquisition of that knowledge could be particularly useful to understand the pathogenesis of acquired and congenital diseases. In the last few years, with the Telethon support we have analyzed and partially characterized the transcription factors involved in p73 modulation in differentiation. P73 was recently identified as a homolog of p53. P73 null mice exhibit defect in differentiation and development of central nervous system. Our group has recently identified that is a target gene for deltaEF1 family members (deltaEF1 and SIP1). Mutations of SIP1 protein are present in patients affected by Mowat-Wilson syndrome, that resemble defects similar to p73 null mice. We propose to study the molecular mechanisms that underlye the transcriptional control of p73 by deltaEF1 family members. Moreover we will analyze whether mutant SIP1 proteins are defective in the ability to modulate p73. These studies could clarify in more detail the mechanisms underlying embryogenesis and might be useful for the comprehension of Mowat-Wilson syndrome defects.