Molecular investigation of the role of CDKN1C (p57KIP2) and its mutations in adrenal development and tumor

• Grant number: 12/09391-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: November 01, 2012
• End date: October 31, 2013
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Luiz Gonzaga Tone
• Grantee: Kleiton Silva Borges
• Supervisor: Eric Vilain
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of California, Los Angeles (UCLA), United States
• Associated to the scholarship: 10/08699-5 - Mechanisms involved in the inhibition of aurora-kinases in adrenal carcinoma, BP.DR

Abstract

CDKN1C (p57KIP2) is a cyclin-dependent kinase inhibitor, member of the CIP/KIP family, which includes p21 and p27. CDKN1C and is located at the chromosomal locus 11p15. p57KIP2 presents higher expression levels during organogenesis, however its expression disappears after birth, except for adrenal cortex. In this case, its expression is maintained in the adult organ and its silencing is associated with adrenocortical carcinoma. Recently, the Dr. Vilain's group (University of California, Los Angeles - UCLA) has found missense mutations on PCNA-binding site of CDKN1C gene that result in IMAGe syndrome. IMAGe syndrome (Intrauterine growth restriction, Metaphyseal dysplasia, Adrenal hypoplasia congenita, and Genital anomalies) is an undergrowth developmental disorder with life-threatening condition. Preliminary results show that these mutations inhibit PCNA binding in CDKN1C and cause monoubiquitination of this protein. Although several molecular consequences are involved with these events, molecular effects of IMAGe mutations need to be elucidated, since them, among other things, are associated with adrenal abnormalities. Based on these findings, the aim of this project is investigating thought in vitro and in vivo assays the role of CDKN1C and its mutations in adrenal development and tumor. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BORGES, KLEITON S.; ARBOLEDA, VALERIE A.; VILAIN, ERIC. Mutations in the PCNA-binding site of CDKN1C inhibit cell proliferation by impairing the entry into S phase. CELL DIVISION, v. 10, MAR 28 2015. (12/09391-0)