Role of the beta isoform of 14-3-3 proteins in cellular proliferation and oncogenic transformation.

Abstract:

:The 14-3-3 proteins are associated with proto-oncogene and oncogene products. Here, we generated NIH 3T3 cells overexpressing the beta isoform of the 14-3-3 proteins (14-3-3 beta) to examine the function of this isoform in cellular proliferation and oncogenic transformation. Overexpression of 14-3-3 beta in NIH 3T3 cells stimulated cell growth and supported anchorage-independent growth in soft agar medium and tumor formation in nude mice. To elucidate the molecular mechanisms of 14-3-3 beta-mediated NIH 3T3 transformation, we examined the activity of mitogen-activated protein kinase (MAPK) after serum stimulation. Overexpression of 14-3-3 beta augmented MAPK activity after serum stimulation, and MAPK activity correlated well with the amount of 14-3-3 beta expression. The colony-forming ability of NIH 3T3 cells overexpressing 14-3-3 beta in soft agar medium was efficiently abolished by exogenous expression of a dominant-negative mutant of MEK1 and 14-3-3 beta physically interacted with Raf-1 in these cells. These findings indicate that 14-3-3 beta has oncogenic potential, mainly through enhancement of Raf-1 activation and resultant augmentation of signaling in the MAPK cascade.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Takihara Y,Matsuda Y,Hara J

doi

10.1093/carcin/21.11.2073

keywords:

subject

Has Abstract

pub_date

2000-11-01 00:00:00

pages

2073-7

issue

11

eissn

0143-3334

issn

1460-2180

journal_volume

21

pub_type

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