Nucleolar release of Hand1 acts as a molecular switch to determine cell fate

@article{Martindill2007NucleolarRO,
  title={Nucleolar release of Hand1 acts as a molecular switch to determine cell fate},
  author={David Michael John Martindill and Catherine A. Risebro and Nicola Smart and Maria Del Mar Franco-Viseras and Carla O. Rosario and Carol Jane Swallow and James W. Dennis and Paul Richard Riley},
  journal={Nature Cell Biology},
  year={2007},
  volume={9},
  pages={1131-1141}
}
The bHLH transcription factor Hand1 is essential for placentation and cardiac morphogenesis in the developing embryo. Here we implicate Hand1 as a molecular switch that determines whether a trophoblast stem cell continues to proliferate or commits to differentiation. We identify a novel interaction of Hand1 with a protein that contains an I-mfa (inhibitor of myogenic factor) domain that anchors Hand1 in the nucleolus where it negatively regulates Hand1 activity. In the trophoblast stem-cell… 

Developmental regulation of Hand1 via nucleolar sequestration

TLDR
Findings are presented that describe a novel mode of Hand1 regulation that is a crucial step in trophoblast stem cell differentiation and placentation and support previous studies that implicate the nucleolus as a molecular 'sink'.

Cell cycle switch to endocycle: The nucleolus lends a hand

TLDR
The wider implications of the findings are examined, some of the unanswered questions that remain are addressed and the ‘molecular switch’ that promotes mitotic cell cycle exit and the onset of endoreduplication is addressed.

C. elegans Nucleostemin Is Required for Larval Growth and Germline Stem Cell Division

TLDR
The data support a role for C. elegans nucleostemin in cell growth and proliferation by promoting ribosome biogenesis.

A bHLH Code for Cardiac Morphogenesis

TLDR
The goal is to review what is currently known and address strategies for gaining further understanding of Hand/Twist gene dosage and functional redundancy relationships within the developing heart that may underlie congenital heart defect pathogenesis.

Cell fate in the Hand of Plk4

TLDR
The transcription factor Hand1 is required for cell-fate determination during placental development and this switch is controlled by the antagonistic activities of HICp40 and Polo-like kinase-4 (Plk4).

Polo-like kinase 4 maintains centriolar satellite integrity by phosphorylation of centrosomal protein 131 (CEP131)

TLDR
It is observed that although PLK4-mediated phosphorylation of Ser-78 is dispensable for CEP131 localization, ciliogenesis, and centriole duplication, it is essential for maintaining the integrity of centriolar satellites.

Nuclear Translocation of Hand-1 Acts as a Molecular Switch to Regulate Vascular Radiosensitivity in Medulloblastoma Tumors: The Protein uPAR Is a Cytoplasmic Sequestration Factor for Hand-1

TLDR
It is shown that uPAR protein acts as a cytoplasmic sequestration factor for a novel basic helix-loop-helix transcription factor, Hand-1, which plays an essential role in the differentiation of trophoblast giant cells and cardiac morphogenesis.

CAF-1 p150 and Ki-67 Regulate Nuclear Structure Throughout the Human Cell Cycle

TLDR
Together, these studies indicate that p150N coordinates the three-dimensional arrangement of both interphase and mitotic chromosomes via Ki-67, a protein widely used as a clinical marker of cellular proliferation.

A novel role for Plk4 in regulating cell spreading and motility

TLDR
A gene expression pattern predictive of reduced motility in Plk4+/− murine embryonic fibroblasts (MEFs) is identified and an unexpected activity of PlK4 that promotes cell migration is revealed that may underlie an association between increased Plk 4 expression, cancer progression and death from metastasis in solid tumor patients.
...

References

SHOWING 1-10 OF 55 REFERENCES

The Hand1 bHLH transcription factor is essential for placentation and cardiac morphogenesis

TLDR
Handl, previously called Hxt, eHAND and Thingl, encodes a basic helix-loop-helix (bHLH) transcription factor that starts to be expressed during pre-implantation development and is essential for differentiation of both trophoblast and cardiomyocytes, which are embryologically distinct cell lineages.

The HAND1 Basic Helix-Loop-Helix Transcription Factor Regulates Trophoblast Differentiation via Multiple Mechanisms

TLDR
It is concluded that development of the trophoblast lineage is regulated by the interacting functions of HAND1, MASH2, and their cofactors.

Sak/Plk4 and mitotic fidelity

TLDR
It is suggested that Sak provides feedback to cell cycle regulators, and thereby precision to the switch-like transitions of centrosome duplication and exit-from-mitosis to contribute to improvements in cancer risk assessment and novel therapies.

Reprogramming the cell cycle for endoreduplication in rodent trophoblast cells.

TLDR
Several points at which cell cycle regulation could be targeted to shift cells from a mitotic to an endoreduplicative cycle are suggested.

Nucleolar Sequestration of RelA (p65) Regulates NF-κB-Driven Transcription and Apoptosis

TLDR
This work identifies a novel cellular mechanism for regulating NF-κB-driven transcription and apoptosis, involving the nucleolar sequestration of a key NF-γB subunit and identifies an N-terminal motif of RelA that is essential for the nucleoli localization of the protein.

Requirement of the mouse I‐mfa gene for placental development and skeletal patterning

TLDR
In situ hybridization analysis demonstrated that mouse I‐mfa was highly expressed in extraembryonic lineages, in the sclerotome, and subsequently within mesenchymal precursors of the axial and appendicular skeleton, before chondrogenesis occurs.

Differential Regulation of Hand1 Homodimer and Hand1-E12 Heterodimer Activity by the Cofactor FHL2

TLDR
A novel differential regulation of Hand1 heterodimers versus homodIMers by association of the cofactor FHL2 is described and insight is provided into the potential for a tertiary level of control of Hand 1 activity in the developing heart.

Late mitotic failure in mice lacking Sak, a polo-like kinase

Identification of a cryptic nucleolar-localization signal in MDM2

TLDR
An NoLS in the carboxy-terminal region of human MDM2 that does not function in unstressed cells, but is necessary to cooperate with nucleolar-localization signals in p14 to allow relocalization of both proteins is identified.
...