NM23-H1 Tumor Suppressor and Its Interacting Partner STRAP Activate p53 Function

Abstract

Similarly, NM23-H1 and STRAP stimulated p53-induced apoptosis and growth inhibition, whereas the NM23-H1(C145S) and STRAP(C152S/C270S) mutants had no effect. We also demonstrated that p53 activation by NM23-H1 and STRAP was mediated by removing Mdm2, a negative regulator of p53, from the p53-Mdm2 complex. These results suggest that NM23-H1 and its interacting partner STRAP physically interact with p53 and positively regulate its functions, including p53-induced apoptosis and cell cycle arrest.

Targeting Tumor Metastasis by Regulating Nm23 Gene Expression

“…These genes encode the A and B subunits respectively of NDPK. Nm23 family protein involves in multiple biological functions in cell adhesion, cell migration, cellular differentiation, microtubule polymerization, signal transduction pathway, histidine dependent phosphorylation, vascular invasion, endocytosis, tumor cell shape and in apoptosis (Kimura et al, 2000;Krishnan et al, 2001;Otsuki et al, 2001;Fournier et al, 2003;Gallagher et al, 2003;Narayanan and Ramaswami, 2003;Sirotkovic-Skerley et al, 2005;Jung and Seong, 2007). Scientific evidence suggests that Nm23 has a dual role in tumor progression: i) over expression in primary tumors at early stages, ii) the association between the loss of Nm23-H1 expression in later stages and tumor aggressiveness and metastatic potential.…”

Serine-Threonine Kinase Receptor-associated Protein Inhibits Apoptosis Signal-regulating Kinase 1 Function through Direct Interaction

“…In Vivo and in Vitro Binding Assays-In vivo binding assays were performed as previously described using HEK293, NIH 3T3, or HeLa cells transiently transfected with the indicated expression vectors (11,(23)(24)(25). To determine the direct interaction between ASK1 and STRAP, a GST pull-down assay was also performed using recombinant ASK1 and STRAP proteins as described (27).…”

“…STRAP also contributes to tumor progression by blocking TGF-␤-mediated signaling, especially in colon and lung carcinomas, indicating the possible involvement of STRAP in tumorigenesis (20,22). STRAP can also interact directly with p53 and stimulate p53-mediated signaling, implying that STRAP may function as a tumor suppressor in cells (23).…”

Nanoparticle delivery of anti-metastatic NM23-H1 gene improves chemotherapy in a mouse tumor model

“…[31][32][33] Recent studies showed that NM23-H1 and its interacting partner STRAP physically interact with p53 and positively regulate its functions, including p53-induced apoptosis and cell cycle arrest. 34 In this study, we evaluated the inhibition of tumor metastasis in melanoma tumor-bearing mice by delivery of IONP-PLL carrying an expression plasmid with the NM23-H1 gene. The efficacy of the IONP-PLL treatment was tested both in isolation and in combination with conventional chemotherapy.…”