A novel Hansenula polymorpha transcriptional factor HpHAP4‐B, able to functionally replace the S. cerevisiae HAP4 gene, contains an additional bZip motif

Sybirna, Kateryna; Petryk, Nataliya; Zhou, You Fang; Sibirny, Andriy А.; Bolotin‐Fukuhara, Monique

doi:10.1002/yea.1802

Cited by 8 publications

(21 citation statements)

References 45 publications

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“…9). The iron-dependent regulation of CAP2 expression was first noted in a C. albicans microarray study (14), and indeed for CAP2 orthologs in other systems as well (17,21,79). In iron-replete media, although the CAP2 mRNA level was diminished to a low basal level, the Cap2 protein level was reduced to an undetectable level (Fig.…”

Section: Transcriptional Regulation Of Cap2 Expressionsupporting

confidence: 52%

“…Complex-There are previous reports that Cap2 or its orthologs likely function in a complex with Hap2-Hap3-Hap5 (19,21,29). In a previous study, three HAP4-like genes and two HAP3-like genes were identified in the C. albicans genome (27).…”

Section: Cap2-dependent Up-regulation Of Components Of the Hap Regulamentioning

confidence: 96%

“…15 and 16). In addition, the regulation of iron homeostasis in fungal genomes, including C. albicans, is dependent on the HAP regulatory complex (17)(18)(19)(20)(21). In S. cerevisiae, the HAP complex components Hap2, Hap3, and Hap5, are homologous to mammalian NF-YA, NF-YB, and NF-YC subunits, respectively, of the trimeric CCAAT box binding regulator NF-Y (22).…”

Section: From the School Of Life Sciences Jawaharlal Nehru Universitmentioning

confidence: 99%

“…Barring Saccharomyces genomes, other fungal genomes studied (17,21,26,27) lacked a full-length Hap4 protein. Instead, HapX from A. nidulans (17) and Php4 from Schizosaccharomyces pombe (18) contained the short 17-amino acid HAP4-like (HAP4L) domain.…”

Section: From the School Of Life Sciences Jawaharlal Nehru Universitmentioning

confidence: 99%

“…The S. cerevisiae Hap5 protein contains a conserved Hap4 interaction domain, required for interaction with Hap4 (29). The interaction of Hansenula polymorpha Hap4a and Hap4b proteins with Hap5 has also been demonstrated using the yeast two-hybrid assay (21). Furthermore, HapX interaction has also been uncovered with the HAP2-HAP3-HAP5 complex using bimolecular fluorescence complementation assay (17).…”

Section: From the School Of Life Sciences Jawaharlal Nehru Universitmentioning

confidence: 99%

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Cap2-HAP Complex Is a Critical Transcriptional Regulator That Has Dual but Contrasting Roles in Regulation of Iron Homeostasis in Candida albicans

Singh¹,

Prasad²,

Sinha³

et al. 2011

Journal of Biological Chemistry

100

211

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Iron homeostasis is highly regulated in organisms across evolutionary time scale as iron is essential for various cellular processes. In a computational screen, we identified the Yap/bZIP domain family in Candida clade genomes. Cap2/Hap43 is essential for C. albicans growth under iron-deprivation conditions and for virulence in mouse. Cap2 has an amino-terminal bipartite domain comprising a fungal-specific Hap4-like domain and a bZIP domain. Our mutational analyses showed that both the bZIP and Hap4-like domains perform critical and independent functions for growth under iron-deprivation conditions. Transcriptome analysis conducted under iron-deprivation conditions identified about 16% of the C. albicans ORFs that were differentially regulated in a Cap2-dependent manner. Microarray data also suggested that Cap2 is required to mobilize iron through multiple mechanisms; chiefly by activation of genes in three iron uptake pathways and repression of iron utilizing and iron storage genes. The expression of HAP2, HAP32, and HAP5, core components of the HAP regulatory complex was induced in a Cap2-dependent manner indicating a feed-forward loop. In a feed-back loop, Cap2 repressed the expression of Sfu1, a negative regulator of iron uptake genes. Cap2 was coimmunoprecipitated with Hap5 from cell extracts prepared from iron-deprivation conditions indicating an in vivo association. ChIP assays demonstrated Hap32-dependent recruitment of Hap5 to the promoters of FRP1 (Cap2-induced) and ACO1 (Cap2-repressed). Together our data indicates that the Cap2-HAP complex functions both as a positive and a negative regulator to maintain iron homeostasis in C. albicans.

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Section: Transcriptional Regulation Of Cap2 Expressionsupporting

confidence: 52%

Section: Cap2-dependent Up-regulation Of Components Of the Hap Regulamentioning

confidence: 96%

Section: From the School Of Life Sciences Jawaharlal Nehru Universitmentioning

confidence: 99%

Section: From the School Of Life Sciences Jawaharlal Nehru Universitmentioning

confidence: 99%

Section: From the School Of Life Sciences Jawaharlal Nehru Universitmentioning

confidence: 99%

See 3 more Smart Citations

Cap2-HAP Complex Is a Critical Transcriptional Regulator That Has Dual but Contrasting Roles in Regulation of Iron Homeostasis in Candida albicans

Singh¹,

Prasad²,

Sinha³

et al. 2011

Journal of Biological Chemistry

100

211

View full text Add to dashboard Cite

show abstract

Thirty years of the HAP2/3/4/5 complex

Bolotin‐Fukuhara

2017

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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The CCAAT-Binding Complex Controls Respiratory Gene Expression and Iron Homeostasis in Candida Glabrata

Thiébaut

Delaveau

Benchouaia

et al. 2017

Sci Rep

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The CCAAT-binding complex (CBC) is a heterotrimeric transcription factor which is widely conserved in eukaryotes. In the model yeast S. cerevisiae, CBC positively controls the expression of respiratory pathway genes. This role involves interactions with the regulatory subunit Hap4. In many pathogenic fungi, CBC interacts with the HapX regulatory subunit to control iron homeostasis. HapX is a bZIP protein which only shares with Hap4 the Hap4Like domain (Hap4L) required for its interaction with CBC. Here, we show that CBC has a dual role in the pathogenic yeast C. glabrata. It is required, along with Hap4, for the constitutive expression of respiratory genes and it is also essential for the iron stress response, which is mediated by the Yap5 bZIP transcription factor. Interestingly, Yap5 contains a vestigial Hap4L domain. The mutagenesis of this domain severely reduced Yap5 binding to its targets and compromised its interaction with Hap5. Hence, Yap5, like HapX in other species, acts as a CBC regulatory subunit in the regulation of iron stress response. This work reveals new aspects of iron homeostasis in C. glabrata and of the evolution of the role of CBC and Hap4L-bZIP proteins in this process.

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A novel Hansenula polymorpha transcriptional factor HpHAP4‐B, able to functionally replace the S. cerevisiae HAP4 gene, contains an additional bZip motif

Cited by 8 publications

References 45 publications

Cap2-HAP Complex Is a Critical Transcriptional Regulator That Has Dual but Contrasting Roles in Regulation of Iron Homeostasis in Candida albicans

Cap2-HAP Complex Is a Critical Transcriptional Regulator That Has Dual but Contrasting Roles in Regulation of Iron Homeostasis in Candida albicans

Thirty years of the HAP2/3/4/5 complex

The CCAAT-Binding Complex Controls Respiratory Gene Expression and Iron Homeostasis in Candida Glabrata

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