NRF2 SUMOylation promotes de novo serine synthesis and maintains HCC tumorigenesis.

Nuclear factor erythroid-2 related factor 2 (NRF2) is a pivotal transcription factor that maintains cellular redox homeostasis and facilitates the development of malignant tumor phenotypes. At the molecular level, NRF2 promotes de novo serine synthesis and SUMOylation affects its function. Our results indicated that the SUMO1 acceptor site of NRF2 is the conserved lysine residue 110 (K110), and that NRF2 SUMOylation deficiency inhibited tumorigenesis in hepatocellular carcinoma (HCC).

Cell Transformation by PTP1B Truncated Mutants Found in Human Colon and Thyroid Tumors.

Expression of wild-type protein tyrosine phosphatase (PTP) 1B may act either as a tumor suppressor by dysregulation of protein tyrosine kinases or a tumor promoter through Src dephosphorylation at Y527 in human breast cancer cells. To explore whether mutated PTP1B is involved in human carcinogenesis, we have sequenced PTP1B cDNAs from human tumors and found splice mutations in ~20% of colon and thyroid tumors. The PTP1BΔE6 mutant expressed in these two tumor types and another PTP1BΔE5 mutant expressed in colon tumor were studied in more detail.

Induction of SENP1 in myocardium contributes to abnormities of mitochondria and cardiomyopathy.

Defect in mitochondrial biogenesis and cardiac energy metabolism is a critical contributing factor to cardiac hypertrophy and heart failure. Sentrin/SUMO specific protease 1 (SENP1) mediated regulation of PGC-1α transcriptional activity plays an essential role in mitochondrial biogenesis and mitochondrial function. However, whether SENP1 plays a role in cardiac hypertrophy and failure is unknown.

SUMOylation attenuates human β-arrestin 2 inhibition of IL-1R/TRAF6 signaling.

β-Arrestin 2 as an adaptor plays a role in the regulation of receptor desensitization, trafficking, and signaling. Bovine β-arrestin 2 has been shown to be SUMOylated on the lysine 400 residue, which links it to the endocytosis of the β2-adrenergic receptor. Here we identify a major SUMOylation site, lysine 295, on human β-arrestin 2.

Small ubiquitin-like modifier (SUMO) protein-specific protease 1 de-SUMOylates Sharp-1 protein and controls adipocyte differentiation.

Adipocyte differentiation is regulated by a transcriptional cascade that mainly includes CCAAT/enhancer-binding protein family members and the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ). Here we show the defects in adipocyte differentiation as well as PPARγ expression in Senp1(-/-) mouse embryonic fibroblast cells induced by adipogenic stimuli. We further determine that SENP1 is a specific de-SUMOylation protease for Sharp-1, a repressor for PPARγ transcription and adipogenesis.

Co-expression of P1A35-43/beta2m fusion protein and co-stimulatory molecule CD80 elicits effective anti-tumor immunity in the P815 mouse mastocytoma tumor model.

A strong CTL response is dependent upon a high level of expression of specific class I major histocompatibility complex (MHC)/peptide complexes at the cell surface. An epitope-linked beta2-microglobulin (beta2m) molecule could provide a simple and more efficient means to enhance the formation of defined MHC/peptide complexes. However, the ability of an epitope-linked beta2m molecule to elicit primary CTL responses in vivo is still unknown.

Tumor-specific, hypoxia-regulated, WW domain-containing oxidoreductase-expressing adenovirus inhibits human non-small cell lung cancer growth in vivo.

An elevated level of hypoxia-inducible factor 1 (HIF-1) is common in solid tumors and correlates with poor prognosis. Therefore, targeting of HIF-1 presents an appealing approach for cancer therapy. In this study, we developed an adenoviral vector carrying a fusion of human WW domain-containing oxidoreductase (hWWOX) and the HIF-1alpha oxygen-dependent degradation domain (ODD) under the control of a synthetic human recombinant telomerase reverse transcriptase promoter (hrTRTP).

[Activity analysis of human beta β2-microglobulin gene promoter in P815 cells].

Aim: To clone the human beta2-microglobulin(beta2m) gene promoter and study its activity in P815 cells.

Methods: PCR amplification was performed using primers based on human beta2m gene sequence from GenBank and human genomic DNA as a template. The PCR product was directedly ligated into pBluescript II vector for sequencing.