Characterization of HKE2: an ancient antigen encoded in the major histocompatibility complex

Abstract

Genes at the centromeric end of the human leukocyte antigen region influence adaptive autoimmune diseases and cancer. In this study, we characterized protein expression of HKE2, a gene located in the centromeric portion of the class II region of the major histocompatibility complex encoding subunit 6 of prefoldin. Immunohistochemical analysis using an anti-HKE2 antibody indicated that HKE2 protein expression is dramatically upregulated as a consequence of activation. In a tissue microarray and in several tumors, HKE2 was overexpressed in certain cancers compared with normal counterparts. The localization of the HKE2 gene to the class II region, its cytoplasmic expression and putative protein-binding domain suggest that HKE2 may function in adaptive immunity and cancer.

Identification of prefoldin amplification (1q23.3-q24.1) in bladder cancer using comparative genomic hybridization (CGH) arrays of urinary DNA

“…This is relevant in cancer research since members of the actin-related protein family requiring the PFND2 pathway for their proper maturation play a role in a variety of key cellular events, including orientation of the spindle during mitosis, nuclear migration [46], membrane polarity and endocytosis [47], or transcriptional regulation [48,49]. The amplification and overexpression results presented in this report correlating between them and with increased proliferation rates are consistent with the upregulation of members of the PFND2 protein family in cells and tumors of different origin such as glioblastoma [50], breast [51], pancreatic [52], or colon [53], where they are believed to play an oncogenic role [54-56]. With this biological relevant information, PFND2 was selected because of availability of reagents to be optimized for its assessment in bladder tumors.…”

Ophiobolin A Induces Autophagy and Activates the Mitochondrial Pathway of Apoptosis in Human Melanoma Cells

“…Prefoldins (PFDs) [33] are hetero-oligomer chaperones involved in cancer development, since their main targets are actin and tubulin [33]. Up-regulation of members of the PFD protein family has been reported in different tumours, such as glioblastoma [34], breast [35], pancreatic [36], colon [37], bladder [38] and cervical [39] carcinomas. The heat shock proteins (HSPs) [40] have been reported to be significantly elevated in many kind of human cancers and their over-expression has been correlated to therapeutic resistance and poor survival.…”

The HLA genomic loci map: expression, interaction, diversity and disease

“…41 PFDN6 encodes prefoldin subunit 6, and the gene was reported to be overexpressed in certain cancers compared with normal counterparts in a tissue microarray study. 42 Thirty-three of the non-HLA expressed genes (GABBR1, MOG, ZNRD1, RNF39, TRIM10, TRIM39, PRR3, ABCF1, DDR1, CCHCR1, TCF19, POU5F1, BAT1, ATP6V1G2, LTB, LST1, AIF1, BAT3, MSH5, EHMT2, STK19, CYP21A2, TNXB, PPT2, AGPAT1, AGER, TAP2, PSMB8, PSMB9, BRD2, COL11A2, SLC39A7 and TAPBP) and HLA-F appear to express spliced variants with an overall average of 2.6 different kinds of spliced variants per gene. One of the recently identified expressed genes with a relatively large number of spliced variants is C6orf25 that is located between LY6G6C and DDAH2 within the class III region.…”