The Complex Regulation of HIC (Human I-mfa Domain Containing Protein) Expression

Abstract

Human I-mfa domain containing protein (HIC) differentially regulates transcription from viral promoters. HIC affects the Wnt pathway, the JNK/SAPK pathway and the activity of positive transcription elongation factor-b (P-TEFb). Studies exploring HIC function in mammalian cells used ectopically expressed HIC due to undetected endogenous HIC protein. HIC mRNA contains exceptionally long 5′ and 3′ untranslated regions (UTRs) compared to the average length of mRNA UTRs. Here we show that HIC protein is subject to strict repression at multiple levels. The HIC mRNA UTRs reduce the expression of HIC or of a reporter protein: The HIC 3′-UTR decreases both HIC and reporter mRNA levels, whereas upstream open reading frames located in the 5′-UTR repress the translation of HIC or of the reporter protein. In addition, ectopically expressed HIC protein is degraded by the proteasome, with a half-life of approximately 1 h, suggesting that upon activation, HIC expression in cells may be transient. The strict regulation of HIC expression at the levels of mRNA stability, translation efficiency and protein stability suggests that expression of the HIC protein and its involvement in the various pathways is required only under specific cellular conditions.

Inhibitor of myogenic differentiation family isoform a, a new positive regulator of fibronectin production by glomerular mesangial cells

“…Earlier studies have demonstrated that I-mfa plays an important role in the inhibition of myogenesis (8), skeletogenesis (25,53), and osteoclastogenesis (37). I-mfa may also function as a tumor suppressor gene (27,28,43). The present study provided evidence, for the first time, that I-mfa is also present and functional in kidney cells.…”

Intermolecular masking of the HIV-1 Rev NLS by the cellular protein HIC: Novel insights into the regulation of Rev nuclear import

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