Up-regulation of CIR1/CROC1 expression upon cell immortalization and in tumor-derived human cell lines

Abstract

Acquisition of the immortal phenotype by tumor cells represents an essential and potentially rate-limiting step in tumorigenesis. To identify changes in gene expression that are associated with the early stages of cell immortalization, we compared genetically matched pairs of pre-immortal and immortal human cell clones by mRNA di erential display. Two transcripts, denoted CIR1 and CIR2, were identi®ed which were up-regulated in immortal cells. Sequence analysis revealed CIR1 to be identical to the recently cloned CROC1/UEV-1 gene, whereas CIR2 corresponds to an as yet uncharacterized 1.2 kb mRNA. A 5 ± 6-fold elevation in CIR1/CROC1 expression and a 2 ± 3-fold elevation in CIR2 expression were observed in SV40-transformed human enbryonic kidney cells immediately following proliferative crisis, suggesting a potential role for these genes in immortalization. Expression of CIR1/CROC1 was found to be elevated also in a variety of immortal human tumorderived cell lines, as compared to their normal tissue counterparts. These results are compatible with induction of CIR1/CROC1 being an early event in the acquisition of immortality and with a role for this gene in the immortal phenotype of tumor cells.

Uev1A, a ubiquitin conjugating enzyme variant, inhibits stress-induced apoptosis through NF-κB activation

“…The anti-apoptotic phenotype of Uev1A overexpressed cells could be partly due to the result of induced expression of Bcl-2 by the persistent activation of NF-κB in these cells. We suggest that the elevation of basal-level NF-κB activity upon stable overexpression of UEV1A can mimic the phenomena of chronic inflammation and that this observation is consistent with previous reports [1][2][3]5] pointing to UEV1 as a candidate protooncogene. Down-regulation of UEV1 with RNAi reversed NF-κB activation in the UEV1A overexpression cell lines; this down-regulation was accompanied by elevated apoptosis upon stresses.…”

“…It was initially reported as a transactivator of the c-fos promoter [1]. UEV1 was independently isolated by two mRNA differential display screens, and was found to be down-regulated in HT-29-M cells undergoing differentiation [2], and up-regulated when SV40-transformed human embryonic kidney cells become immortal [3]. UEV1 was also identified as a putative homolog of the yeast MMS2 involved in DNA postreplication repair [4], and found to be variously up-regulated in all tumor cell lines examined [5].…”

Eukaryotic DNA damage tolerance and translesion synthesis through covalent modifications of PCNA

“…Sequence and functional homologs of all proteins involved in error-free DDT, including Mms2 [140], Ubc13 [141] and Rad5 [142,143], have been found in mammals, plants and other higher eukaryotes [144,145]. For a few limited examples, suppression of the above genes resulted in phenotypes reminiscent of the corresponding yeast mutants [143,146,147].…”

The protein profile of acetazolamide-treated sera in mice bearing Lewis neoplasm

“…Both hMMS2 and CROC1 are able to complement the yeast MMS2 null mutant with respect to its sensitivity to DNA damaging agents (Rothofsky and Lin, 1997). Yeast MMS2 is an Ubc variant and plays an important role in error-free DNA postreplicational repair to protect cells from killing by DNA damaging agents and mutagenesis (Ma et al, 1998;Xiao et al, 1998). CROC1 (contingent replication of cDNA-1) was originally isolated in a screen to identify cDNAs that transactivates the c-fos promoter (Sancho et al, 1998).…”