ERp57/PDIA3 A PLEIOTROPIC MEMBER OF THE PDIs FAMILY

Session

Pharmaceutical and Natural Sciences

Description

Protein disulfide isomerases (PDIs) are an important cellular oxidoreductase enzyme family including several structurally related components. PDIs are involved in protein folding, catalyzing the formation and remodeling of disulfide bonds, and are mainly located in the endoplasmic reticulum (ER). The ERp57/PDIA3 has a noncanonical ER retention signal (QEDL) on the C-terminal domain and a Lys-rich nuclear localization signal, which binds with high affinity to a specific site of importin, responsible for the nuclear import process [1]. ERp57/PDIA3, found in different extracellular and subcellular locations, is involved in multiple processes [2,3].

The nuclear localization of ERp57/PDIA3 was discovered many years ago, nevertheless, its role in the nucleus is not well understood. It has been shown that ERp57/PDIA3 altered in different cancer cell lines. This protein participates in the signal transduction processes of STAT3 pathways [4,5], and binds specific DNA fragments in a melanoma cell line [6]. In respect of its localization on the plasma membrane, the ERp57/PDIA3 seems involved in EGFR signaling and internalization, as evidenced by the silencing of ERp57/PDIA3 in MDA-MB-468 cells [7] and it was identified also as an alternative cell membrane receptor for active forms of vitamin D3 that regulates some phenotypic functions and nongenomic response [8,9]. More recently it has been hypothesized as a pharmacological target in glioblastoma because ERp57/PDIA3 inhibition induced cytotoxic effects in two different glioblastoma cell lines (T98G and U-87 MG cells)[10]. Its involvement in cancer progression and other diseases suggests a potential use of ERp57/PDIA3 both as a marker and a therapeutic target. ERp57/PDIA3 is an important research target considering its various subcellular locations and its involvement in the cellular response.

Proceedings Editor

Edmond Hajrizi

ISBN

978-9951-550-95-6

Location

UBT Lipjan, Kosovo

Start Date

28-10-2023 8:00 AM

End Date

29-10-2023 6:00 PM

DOI

10.33107/ubt-ic.2023.120

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Oct 28th, 8:00 AM Oct 29th, 6:00 PM

ERp57/PDIA3 A PLEIOTROPIC MEMBER OF THE PDIs FAMILY

UBT Lipjan, Kosovo

Protein disulfide isomerases (PDIs) are an important cellular oxidoreductase enzyme family including several structurally related components. PDIs are involved in protein folding, catalyzing the formation and remodeling of disulfide bonds, and are mainly located in the endoplasmic reticulum (ER). The ERp57/PDIA3 has a noncanonical ER retention signal (QEDL) on the C-terminal domain and a Lys-rich nuclear localization signal, which binds with high affinity to a specific site of importin, responsible for the nuclear import process [1]. ERp57/PDIA3, found in different extracellular and subcellular locations, is involved in multiple processes [2,3].

The nuclear localization of ERp57/PDIA3 was discovered many years ago, nevertheless, its role in the nucleus is not well understood. It has been shown that ERp57/PDIA3 altered in different cancer cell lines. This protein participates in the signal transduction processes of STAT3 pathways [4,5], and binds specific DNA fragments in a melanoma cell line [6]. In respect of its localization on the plasma membrane, the ERp57/PDIA3 seems involved in EGFR signaling and internalization, as evidenced by the silencing of ERp57/PDIA3 in MDA-MB-468 cells [7] and it was identified also as an alternative cell membrane receptor for active forms of vitamin D3 that regulates some phenotypic functions and nongenomic response [8,9]. More recently it has been hypothesized as a pharmacological target in glioblastoma because ERp57/PDIA3 inhibition induced cytotoxic effects in two different glioblastoma cell lines (T98G and U-87 MG cells)[10]. Its involvement in cancer progression and other diseases suggests a potential use of ERp57/PDIA3 both as a marker and a therapeutic target. ERp57/PDIA3 is an important research target considering its various subcellular locations and its involvement in the cellular response.