title: Functional compensation of glutathione S-transferase M1 (GSTM1) null by another GST superfamily member, GSTM2.
abstract: The gene for glutathione-S-transferase (GST) M1 (GSTM1), a member of the GST-superfamily, is widely studied in cancer risk with regard to the homozygous deletion of the gene (GSTM1 null), leading to a lack of corresponding enzymatic activity. Many of these studies have reported inconsistent findings regarding its association with cancer risk. Therefore, we employed in silico, in vitro, and in vivo approaches to investigate whether the absence of a functional GSTM1 enzyme in a null variant can be compensated for by other family members. Through the in silico approach, we identified maximum structural homology between GSTM1 and GSTM2. Total plasma GST enzymatic activity was similar in recruited individuals, irrespective of their GSTM1 genotype (positive/null). Furthermore, expression profiling using real-time PCR, western blotting, and GSTM2 overexpression following transient knockdown of GSTM1 in HeLa cells confirmed that the absence of GSTM1 activity can be compensated for by the overexpression of GSTM2.
authors.affiliation: 1] Molecular and Human Genetics Division, Kolkata - 700 032, India [2].
authors.forename: Pritha
authors.initials: P
authors.lastname: Bhattacharjee
authors.forename: Somnath
authors.initials: S
authors.lastname: Paul
authors.forename: Mayukh
authors.initials: M
authors.lastname: Banerjee
authors.forename: Deblina
authors.initials: D
authors.lastname: Patra
authors.forename: Priyam
authors.initials: P
authors.lastname: Banerjee
authors.forename: Nanda
authors.initials: N
authors.lastname: Ghoshal
authors.forename: Arun
authors.initials: A
authors.lastname: Bandyopadhyay
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Giri
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004789:Enzyme Activation; D005260:Female; D015870:Gene Expression; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007527:Isoenzymes; D008297:Male; D008875:Middle Aged; D017385:Sequence Homology; D055815:Young Adult
chemical_list: D005982:Glutathione Transferase; D007527:Isoenzymes; C412602:glutathione S-transferase Mu 2
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