title: PNMA2 mediates heterodimeric interactions and antagonizes chemo-sensitizing activities mediated by members of PNMA family.
abstract: PNMA2, a member of the Paraneoplastic Ma Family (PNMA), was identified through expression cloning by using anti-sera from patients with paraneoplastic disorder. Tissue expression studies showed that PNMA2 was predominantly expressed in normal human brain; however, the protein was shown to exhibit abnormal expression profile as it was found to be expressed in a number of tumour tissues obtained from paraneopalstic patients. The abnormal expression profile of PNMA2 suggests that it might play an important role in tumorigenesis; however, apart from protein expression and immunological studies, the physiological role of PNMA2 remains unclear. In order to determine potential role of PNMA2 in tumorigenesis, and its functional relationship with PNMA family members, MOAP-1 (PNMA4) and PNMA1, expression constructs encoding the respective proteins were generated for both in vitro and in vivo studies. Our investigations showed that over-expressed MOAP-1 and PNMA1 promoted apoptosis and chemo-sensitization in MCF-7 cells as evidenced by condensed nuclei and Annexin-V positive MCF-7 cells; however, the effects mediated by these proteins were significantly inhibited or abolished when co-expressed with PNMA2 in MCF-7 cells. Furthermore, co-immunoprecipitation study showed that PNMA1 and MOAP-1 failed to associate with each other but readily formed respective heterodimer with PNMA2, suggesting that PNMA2 functions as antagonist of MOAP-1 and PNMA1 through heterodimeric interaction.
authors.affiliation: Cancer Biology Group, Department of Biological Sciences, Faculty of Science and Technology, Sunway University, No.5 Jalan Universiti, Bandar Sunway, 47500, Selangor Darul Ehsan, Malaysia.
authors.forename: Yong Hoi
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Cancer Biology Group, Department of Biological Sciences, Faculty of Science and Technology, Sunway University, No.5 Jalan Universiti, Bandar Sunway, 47500, Selangor Darul Ehsan, Malaysia.
authors.forename: Siew Wai
authors.initials: SW
authors.lastname: Pang
authors.affiliation: Cancer Biology Group, Department of Biological Sciences, Faculty of Science and Technology, Sunway University, No.5 Jalan Universiti, Bandar Sunway, 47500, Selangor Darul Ehsan, Malaysia. Electronic address: jefft@sunway.edu.my.
authors.forename: Kuan Onn
authors.initials: KO
authors.lastname: Tan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000941:Antigens / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000737:chemistry; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D019281:Dimerization; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000737:chemistry; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D025941:Protein Interaction Mapping
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000941:Antigens; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C428449:MOAP1 protein, human; C117985:Ma1 antigen; C119249:Ma2 antigen; D009419:Nerve Tissue Proteins; D049452:Green Fluorescent Proteins; D005047:Etoposide
keywords: Chemo-resistance; MOAP-1; PNMA1; PNMA2; Paraneoplastic Ma antigens; Protein interaction