Cell Growth & Differentiation, Vol 3, Issue 4 207-216, Copyright © 1992 by American Association of Cancer Research

ARTICLES

Functional interaction between the two zinc finger domains of the v-erb A oncoprotein

BL Hall, BG Bonde, C Judelson and ML Privalsky
Department of Microbiology, University of California, Davis 95616.

The v-erb A oncogene of avian erythroblastosis virus is a mutated and virally transduced copy of a host cell gene encoding a thyroid hormone receptor. The protein expressed by the v-erb A oncogene binds to DNA and acts as a dominant negative inhibitor of both the thyroid hormone receptor and the closely related retinoic acid receptor. The v-erb A protein has sustained two amino acid alterations within its DNA-binding domain relative to that of c-erb A, one of which, at serine 61, is known to be important for v-erb A function in the neoplastic cell. We report here that the second alteration, at threonine 78, also plays an important, although more indirect, role: alteration of the sequence at threonine 78 such that it resembles that of c-erb A can act as an intragenic suppressor and can partially restore function to a v-erb A protein rendered defective due to a mutation at position 61. Threonine 78 lies within the D-box of the v-erb A protein, a region thought to mediate receptor-receptor dimerizations, and is not in physical proximity to the serine at position 61. It therefore appears that an indirect interaction occurs between these two sites and that this interaction is crucial for v-erb A function.

This article has been cited by other articles:

				T. Schuh, B. Hall, J. Kraft, M. Privalsky, and D Kimelman v-erbA and citral reduce the teratogenic effects of all-trans retinoic acid and retinol, respectively, in Xenopus embryogenesis Development, January 11, 1993; 119(3): 785 - 798. [Abstract] [PDF]