10553

HTATIP2

CC3|SDR44U1|TIP30;HIV-1 Tat interactive protein 2, 30kDa;HTATIP2;HIV-1 Tat interactive protein 2, 30kDa

30 kDa HIV-1 TAT-interacting protein|HIV-1 TAT-interactive protein 2|Tat-interacting protein (30kD)|oxidoreductase HTATIP2|short chain dehydrogenase/reductase family 44U, member 1

11p15.1

protein-coding

Count: 4; Pubmed_search,TAG,Generif,UniProt

PURPOSE: Human TIP30 was initially identified as a candidate metastasis suppressor gene whose expression was down-regulated in human liver, lung, breast, and prostate cancers, and recently the role of this gene was examined in colorectal cancer. The aim of this study was to determine the level of TIP30 expression in colorectal carcinoma (CRC). RESULTS: TIP30 protein levels were lower in colorectal carcinomas compared to normal tissue from the control group (P < 0.001). The frequencies of hypermethylation of TIP30 in tumor were 36%, while there was no aberrant methylation in paired adjacent non-tumor tissue. A statistically significant inverse association was found between TIP30 methylation status and expression of the TIP30 protein in tumor tissues (P = 0.006). Somatic missense mutations in the TIP30 gene were identified in human CRC tissue specimens. CONCLUSIONS: Our results demonstrate that promoter methylation is involved in the decreased expression of TIP30 tumor suppressor gene in human colorectal carcinoma.

CC3 (TIP30) is a protein with pro-apoptotic and anti-metastatic properties. The tumor suppressor effect of CC3 has been suggested to result from inhibition of nuclear transport by binding to importin betas or by regulating transcription through interaction in a complex with co-activator independent of AF-2 function (CIA) and the c-myc gene. Previous biochemical studies indicated that CC3 has protein kinase activity, and a structural similarity to cAMP-dependent protein kinase catalytic subunit was proposed. By contrast, bioinformatics studies suggested a relationship of CC3 to the short chain dehydrogenase reductase family. To clarify details of the CC3 structural family and ligand binding properties, we have determined the crystal structure of CC3 at 1.7-A resolution. CC3 has a short chain dehydrogenase reductase fold and binding specificity for NADPH, yet it is unlikely to be normally enzymatically active because it is monomeric. These structural results, in conjunction with data from earlier mutagenesis work on the nucleotide binding motif, suggest that NADPH binding is important for the biological activity of CC3, including interaction with importins and with the CIA/c-myc system. CC3 provides an example of the adaptation of a metabolic enzyme fold to include a regulatory role, as also seen in the case of the NADH-binding co-repressor CtBP.