N-myristoyltransferase inhibitor protein is homologous to heat shock cognate protein 70.
Many of viral and eukaryotic proteins are required for signal transduction and regulatory functions which undergo a lipid modification by the enzyme N-myristoyltransferase (NMT). In this study, we demonstrated that heat shock cognate protein 70 (HSC70) is homologous to NMT inhibitor protein (NIP71), which was discovered in our laboratory, based on MALDI-TOF mass spectrometric analysis. The purified bovine cytosolic HSC70 and particulate NIP71 produced a dose-dependent inhibition of human NMT having half maximal inhibitions of 235 and 230 nM, respectively. Further, Western blot analysis revealed that the purified particulate NIP71 and cytosolic HSC70 cross-reacted with both anti-NIP71 and anti-HSC70 antibodies. The results we obtained imply that molecular chaperones could be involved in the regulation of NMT in normal and cancerous cells. Further studies directed to revealing the role of HSC70 in the regulation of NMT may lead to the development of gene based therapies of colon cancer.
Selvakumar
Ponniah
P
Department of Pathology, College of Medicine and Research Unit, Saskatchewan Cancer Agency, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 4H4, Canada.
Lakshmikuttyamma
Ashakumary
A
Pasha
Mohammed Khysar
MK
King
Martin J
MJ
Olson
Douglas J H
DJ
Mori
Sumiko
S
Ross
Andrew R S
AR
Hayashi
Kiyoshi
K
Dimmock
Jonathan R
JR
Sharma
Rajendra K
RK
D000217:Acyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; C492718:N-myristoyltransferase inhibitor protein 71, human; D009363:Neoplasm Proteins; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase