PDCD4

Case study 1: Ekaterina Shuvalova, 2021

Programmed cell death 4 protein (PDCD4) regulates many vital cell processes, although is classified as a tumor suppressor because it inhibits neoplastic transformation and tumor growth. PDCD4 is known to inhibit translation initiation by binding to eukaryotic initiation factor 4A and elongation of oncogenic c- and A-myb mRNAs. Additionally, PDCD4 has been shown to interact with poly(A)-binding protein (PABP), which affects translation termination, although the significance of this interaction is not fully understood.

Using in vitro translation systems, the researchers revealed that PDCD4 directly activates translation termination. PDCD4 stimulates peptidyl-tRNA hydrolysis induced by a complex of eukaryotic release factors, eRF1-eRF3. PDCD4 regulates translation termination by facilitating the binding of release factors to the ribosome, increasing the GTPase activity of eRF3, and dissociating eRF3 from the posttermination complex.

Fig1. GTPase activity of eRF3a or eRF3c mixed with 80S and eRF1 in presence/absence of PDCD4.

Fig2. Termi-Luc peptide release assay showing level of peptidyl-tRNA hydrolysis induced by eRF1+eRF3c in the presence/absence of PDCD4.

Case study 2: Yue Li, 2018

Endometriosis (EM) is a kind of estrogen-dependent disease in reproductive-age women. Ovarian EM is the most common type. Although EM is a benign disease, it shares many similar features with cancers. Programmed cell death 4 (PDCD4), a newly identified tumor suppressor, plays an important role in inhibiting tumorigenesis and tumor progression at the transcriptional and translational levels.

To explore the roles of PDCD4 in EM, the researchers detected the expression of PDCD4 in control endometrium and eutopic/ectopic endometrium of ovarian EM patients, and analyzed the effects of PDCD4 on the biological behaviors of endometrial cell lines and primary endometrial cells. PDCD4 effectively inhibited the proliferation and colony-forming ability of endometrial cells maybe by inhibiting cell autophagy. In addition, PDCD4 also suppressed the migration and invasion ability of endometrial cells, the mechanism may be related to NF-κB/MMP2/MMP9 signal pathway.

Fig3. PDCD4 overexpression in HEC-1-A cells had no significant effect on the cell cycle of endometrial cells.

Fig4. The upregulation of PDCD4 could markedly decrease the expression of p-P65, MMP2, and MMP9 in HEC-1-A cells.

Fig1. mTOR signaling pathway.

Fig2. PDCD4 inhibits tumorigenesis through multiple pathways. (Kaikai Lu, 2020)

PDCD4 involved in several pathways and played different roles in them. We selected most pathways PDCD4 participated on our site, such as Proteoglycans in cancer, MicroRNAs in cancer, which may be useful for your reference. Also, other proteins which involved in the same pathway with PDCD4 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

PDCD4 has several biochemical functions, for example, RNA binding, protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by PDCD4 itself. We selected most functions PDCD4 had, and list some proteins which have the same functions with PDCD4. You can find most of the proteins on our site.

PDCD4 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with PDCD4 here. Most of them are supplied by our site. Hope this information will be useful for your research of PDCD4.

EIF4A2; EIF4A1; RELA; EIF4A3; RPS13