HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Identification and characterization of a novel folliculin-interacting protein FNIP2.

Abstract
Birt-Hogg-Dube' syndrome characterized by increased risk for renal neoplasia is caused by germline mutations in the BHD/FLCN gene encoding a novel tumor suppressor protein, folliculin(FLCN), which interacts with FNIP1 and 5'-AMP-activated protein kinase(AMPK). Here we report the identification and characterization of a novel FNIP1 homolog FNIP2 that also interacts with FLCN and AMPK. C-terminally-deleted FLCN mutants, similar to those produced by naturally-occurring germline mutations in BHD patients, were unable to bind FNIP2. These data taken together with our previous results that demonstrated FNIP1 binding to the C-terminus of FLCN suggest that FLCN tumor suppressor function may be facilitated by interactions with both FNIP1 and FNIP2 through its C-terminus. Furthermore, we demonstrate that FNIP1 and FNIP2 are able to form homo- or heteromeric multimers suggesting that they may function independently or cooperatively with FLCN. Differential expression of FNIP1 and FNIP2 transcripts in some normal tissues may indicate tissue specificity for these homologs. Interestingly FNIP1 and FNIP2 were oppositely expressed in human clear cell renal cell carcinoma (RCC), and coordinately expressed in chromophobe RCC and oncocytoma, suggesting their differential function in different histologic variants of RCC.
AuthorsHisashi Hasumi, Masaya Baba, Seung-Beom Hong, Yukiko Hasumi, Ying Huang, Masahiro Yao, Vladimir A Valera, W Marston Linehan, Laura S Schmidt
JournalGene (Gene) Vol. 415 Issue 1-2 Pg. 60-7 (May 31 2008) ISSN: 0378-1119 [Print] Netherlands
PMID18403135 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
Chemical References
  • Carrier Proteins
  • FLCN protein, human
  • FNIP1 protein, human
  • FNIP2 protein, human
  • Multiprotein Complexes
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Tumor Suppressor Proteins
  • Adenylate Kinase
Topics
  • Adenylate Kinase (metabolism)
  • Amino Acid Sequence
  • Carcinoma, Renal Cell (genetics)
  • Carrier Proteins (chemistry, genetics, metabolism)
  • Cell Line
  • Evolution, Molecular
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney (metabolism, pathology)
  • Kidney Neoplasms (genetics)
  • Molecular Sequence Data
  • Multiprotein Complexes (metabolism)
  • Protein Binding
  • Protein Transport
  • Proto-Oncogene Proteins (genetics, metabolism)
  • RNA, Messenger (genetics, metabolism)
  • Sequence Homology, Nucleic Acid
  • Subcellular Fractions (enzymology)
  • Tumor Suppressor Proteins (genetics, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: