The Ustilago maydis Nit2 Homolog Regulates Nitrogen Utilization and Is Required for Efficient Induction of Filamentous Growth

Abstract

Nitrogen catabolite repression (NCR) is a regulatory strategy found in microorganisms that restricts the utilization of complex and unfavored nitrogen sources in the presence of favored nitrogen sources. In fungi, this concept has been best studied in yeasts and filamentous ascomycetes, where the GATA transcription factors Gln3p and Gat1p (in yeasts) and Nit2/AreA (in ascomycetes) constitute the main positive regulators of NCR. The reason why functional Nit2 homologs of some phytopathogenic fungi are required for full virulence in their hosts has remained elusive. We have identified the Nit2 homolog in the basidiomycetous phytopathogen Ustilago maydis and show that it is a major, but not the exclusive, positive regulator of nitrogen utilization. By transcriptome analysis of sporidia grown on artificial media devoid of favored nitrogen sources, we show that only a subset of nitrogen-responsive genes are regulated by Nit2, including the Gal4-like transcription factor Ton1 (a target of Nit2). Ustilagic acid biosynthesis is not under the control of Nit2, while nitrogen starvation-induced filamentous growth is largely dependent on functional Nit2. nit2 deletion mutants show the delayed initiation of filamentous growth on maize leaves and exhibit strongly compromised virulence, demonstrating that Nit2 is required to efficiently initiate the pathogenicity program of U. maydis.

Nitrogen Source Affects Glycolipid Production and Lipid Accumulation in the Phytopathogen Fungus <i>Ustilago maydis</i>

“…Although it is not an oily yeast, U. maydis is able to grow on oily substrates such as free fatty acids, and produce glycolipids upon nitrogen limitation [9] [11] [20] [21]. Our study confirms that under nitrogen-limitation U. maydis produced glycolipids differentially and that nitrogen starvation increases the accumulation of neutral lipids favoring the production of a single type of glycolipid (UA) as reported in the study of Nit2 control which is involved in nitrogen catabolite repression [22]. Additionally, we demonstrated that the glycolipid and fatty acid profile differs in each culture media containing low nitrogen or absence of it.…”

“…For UA a cytochrome P450 monooxygenase Cyp1 catalyzes terminal hydroxylation of palmitic acid and cyp2 is required for subterminal hydroxylation (w-1 hydroxylation) of this fatty acid [1] [12]. The expression of cyp1 is not under nitrogen regulation [22] which implies that UA production can occur without nitrogen source. It has also been reported that the fatty acid profile of MEL contains C14:0, C16:0, C14:1 and C16:1 in U. nuda, but the enzymes involved in the synthesis of this molecule have not been identified [34].…”

NIT2 overexpression predicts poor prognosis in tongue squamous cell carcinoma patients

“…The nitrilase superfamily is divided into 13 branches and is widely distributed in nature [19][20][21]. Human nitrilase (NIT) proteins belong to the nitrilase superfamily and contain two proteins, namely NIT1 (nitrilase-like protein 1) and NIT2 (nitrilase-like protein 2) [21,22].…”

Downregulation of NIT2 inhibits colon cancer cell proliferation and induces cell cycle arrest through the caspase-3 and PARP pathways

“…Human nitrilase (NIT) proteins are members of the nitrilase superfamily that contain a conserved nitrilase domain and thiol enzymes involved in natural product biosynthesis and post-translational modification in plants (5), animals, fungi and certain prokaryotes (6,7). Based on the sequence analysis, the NIT superfamily has been divided into 13 branches (6,8).…”