Punctuated evolution and transitional hybrid network in an ancestral cell cycle of fungi

Medina, Edgar M.; Turner, Jonathan J.; Gordân, Raluca; Buchler, Nicolas E.

doi:10.1101/038372

Cited by 6 publications

(8 citation statements)

References 95 publications

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“…Chytrids share a number of traits with other opisthokonts that are missing from Dikarya, including microtubule-based flagella, 62,63 cells that lack cell walls, and both animal-typical and fungaltypical cell cycle control machinery. 64 Here, we show that chytrid fungi also have an actin regulatory protein repertoire that appears intermediate to that of animals and Dikarya. For example, animals, chytrids, and Dikarya all have a complete Arp2/3 complex; in contrast, all members of the SCAR/WAVE complex, DAAM formins, gelsolin/villin family proteins, talin, and Myo22 (Figures 2 and S2) are conserved in animals and chytrids but are generally missing in the Dikarya.…”

Section: Discussionmentioning

confidence: 71%

The actin networks of chytrid fungi reveal evolutionary loss of cytoskeletal complexity in the fungal kingdom

et al. 2021

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The actin networks of chytrid fungi reveal evolutionary loss of cytoskeletal complexity in the fungal kingdom Highlights d Chytrid fungi diverged before the radiation of Dikarya (multicellular fungi and yeast) d Chytrids have actin genes and structures typical of both Dikarya and animal cells d The regulation of chytrid actin structures resembles that of animal/dikaryotic cells d Presence of a BNI1/BNR1 type formin correlates with the presence of actin cables

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Section: Discussionmentioning

confidence: 71%

The actin networks of chytrid fungi reveal evolutionary loss of cytoskeletal complexity in the fungal kingdom

et al. 2021

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“…Because fungal G1 cyclins are thought to have evolved from a B-type cyclin precursor [18], it is likely that LP docking arose in fungi after their divergence from animals. Consequently, this function could present a target for anti-fungal therapeutics.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, in addition to Cln3 and Cln1/2 cyclin types, some budding yeast species contain a third type of G1 cyclin, called Ccn1, which is also capable of recognizing LP motifs [17]. In contrast, most non-yeast fungi have only a single G1 cyclin (hereafter, "Cln"), which likely diverged prior to the expansion of the budding yeast genes into the three G1 types [18].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of G1 Cyclin Docking Motif Sequences that Control CDK Regulatory Potency In Vivo

et al. 2020

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Cyclin-dependent kinases (CDKs) control the ordered series of events during eukaryotic cell division. The stage at which individual CDK substrates are phosphorylated can be dictated by cyclin-specific docking motifs. In budding yeast, substrates with Leu/Pro-rich (LP) docking motifs are recognized by Cln1/2 cyclins in late G1 phase, yet the key sequence features of these motifs and the conservation of this mechanism were unknown. Here we comprehensively analyzed LP motif requirements in vivo by combining a competitive growth assay with mutational scanning and deep sequencing. We quantified the impact of all single-residue replacements in five different LP motifs, using six distinct G1 cyclins from diverse fungi including medical and agricultural pathogens. The results reveal the basis for variations in potency among wild-type motifs, and allow derivation of a quantitative matrix that predicts the potency of other candidate motifs. In one protein, Whi5, we found overlapping LP and phosphorylation motifs with partly redundant effects. In another protein, the CDK inhibitor Sic1, we found that its LP motif is inherently weak due to unfavorable residues at key positions, and this imposes a beneficial delay in its phosphorylation and degradation. The overall results provide a general method for surveying viable docking motif sequences and quantifying their potency in vivo, and they reveal how variations in LP motif potency can tune the strength and timing of CDK regulation..

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“…Profile-hidden Markov models were built and used to retrieve E2F and pocket protein homologs, as described in ref. 35. Following sequence alignment, phylogenetic analysis was performed using maximum-likelihood methods.…”

Section: Methodsmentioning

confidence: 99%

Conservation and divergence of C-terminal domain structure in the retinoblastoma protein family

Liban

Medina

Tripathi

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The retinoblastoma protein (Rb) and the homologous pocket proteins p107 and p130 negatively regulate cell proliferation by binding and inhibiting members of the E2F transcription factor family. The structural features that distinguish Rb from other pocket proteins have been unclear but are critical for understanding their functional diversity and determining why Rb has unique tumor suppressor activities. We describe here important differences in how the Rb and p107 C-terminal domains (CTDs) associate with the coiled-coil and marked-box domains (CMs) of E2Fs. We find that although CTD-CM binding is conserved across protein families, Rb and p107 CTDs show clear preferences for different E2Fs. A crystal structure of the p107 CTD bound to E2F5 and its dimer partner DP1 reveals the molecular basis for pocket protein-E2F binding specificity and how cyclin-dependent kinases differentially regulate pocket proteins through CTD phosphorylation. Our structural and biochemical data together with phylogenetic analyses of Rb and E2F proteins support the conclusion that Rb evolved specific structural motifs that confer its unique capacity to bind with high affinity those E2Fs that are the most potent activators of the cell cycle.cell cycle | tumor suppressor protein | E2F | protein-protein interactions | evolution E 2F transcription factors regulate the mammalian cell cycle by controlling expression of genes required for DNA synthesis and cell division (1). E2F activity is regulated by the retinoblastoma (Rb) "pocket" protein family members Rb, p107, and p130, which bind and inhibit E2F and recruit repressive factors to E2F-driven promoters (2-5). Beyond cell-cycle regulation, these pocket protein-E2F complexes are the focal point of signaling pathways that trigger diverse cellular processes including proliferation, differentiation, apoptosis, and the stress response. Improper inactivation of pocket proteins is a common mechanism by which cancerous cells maintain aberrant proliferation (1, 5-7). Pocket protein-E2F dissociation and subsequent E2F activation is induced by cyclindependent kinase phosphorylation (3-5, 8) or binding of viral oncoproteins such as the SV40 T-antigen (9).The E2F family contains eight members, five of which (E2F1 to E2F5) form complexes with pocket proteins (1). E2F1 to E2F3 associate exclusively with Rb and are potent activators of transcription during the G1 and S phases of the cell cycle (10, 11). These "activating" E2Fs also specifically induce apoptosis (12). E2F4 is found in complexes with all three pocket proteins and is thought of primarily as a repressor, because it typically occupies promoters of repressed genes and is exported from the nucleus upon release from pocket proteins (1,13,14). In contrast, several studies of E2F4 function during development suggest that E2F4 may stimulate proliferation in certain contexts, acting through association with other transcription factors (14). Better characterization of how E2F4 and E2F5 associate with pocket proteins and other factors is needed to unde...

show abstract

Punctuated evolution and transitional hybrid network in an ancestral cell cycle of fungi

Cited by 6 publications

References 95 publications

The actin networks of chytrid fungi reveal evolutionary loss of cytoskeletal complexity in the fungal kingdom

The actin networks of chytrid fungi reveal evolutionary loss of cytoskeletal complexity in the fungal kingdom

Comprehensive Analysis of G1 Cyclin Docking Motif Sequences that Control CDK Regulatory Potency In Vivo

Conservation and divergence of C-terminal domain structure in the retinoblastoma protein family

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