The NIMA kinase: a mitotic regulator in Aspergillus nidulans and vertebrate cells

K P Lu1, T Hunter

  • 1Molecular Biology and Virology Laboratory, Salk Institute, La Jolla, California 92037, USA.

Progress in Cell Cycle Research
|January 1, 1995
PubMed

Insights

NIMA, a mitotic protein kinase, is essential for cell cycle progression in eukaryotes. Its activation, alongside CDC2, is crucial for triggering mitosis, suggesting NIMA as a key cell cycle regulator.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • CDC2 regulates entry into mitosis in eukaryotic cells.
  • In Aspergillus nidulans, CDC2 activation alone is insufficient for mitosis; NIMA activation is also required.
  • NIMA and CDC2 share analogous functions and regulatory patterns, both impacting the G2/M transition.

Purpose of the Study:

  • To investigate the role of NIMA in eukaryotic cell cycle regulation.
  • To compare the functions and regulation of NIMA and CDC2.
  • To determine if NIMA represents a novel essential cell cycle regulator.

Main Methods:

  • Comparative analysis of NIMA and CDC2 functions in cell cycle progression.
  • Examination of NIMA activity and regulation during the cell cycle.
  • Studies on the effects of NIMA overexpression and dominant-negative mutants in various cell types (Xenopus oocytes, Aspergillus nidulans, human cells).

Main Results:

  • NIMA activity is tightly regulated throughout the cell cycle.
  • NIMA overexpression induces premature mitosis, while dominant-negative mutants cause G2 arrest, similar to CDC2.
  • NIMA and CDC2 exhibit distinct substrate specificities and regulatory mechanisms (intramolecular for NIMA, intermolecular for CDC2).
  • A NIMA-like pathway is vital for the G2/M transition in vertebrate cells.

Conclusions:

  • NIMA is a critical regulator of the G2/M transition in eukaryotic cells.
  • NIMA's distinct regulatory mechanisms and essential role suggest it is a novel cell cycle regulator.
  • Further research is needed to identify NIMA homologues in other species.

Related Concept Videos

DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...