Randy Strich Prep

 

Cyclin C

Nucleus

Mitochondria

Cytoplasm

Cyclin C

Nucleus

Oxidative Stress

Cytoplasm

Cyclin C

Nucleus

Cyclin C

Cytoplasm

Nucleus

Cyclin C

Fis1p: mitochondrial receptor

Mdv1p: adapter protein

DNM1/Drp1: the motor

 

Cytoplasm

Nucleus

Cytoplasm

Cyclin C

Nucleus

Cytoplasm

Cyclin C

Nucleus

Cytoplasm

Programmed cell death

Title Text

  1. In the 2014 paper, they looked at a fis1 deletion mutant based on the idea that cyclin c is binding the the outer membrane of the mitochondria. However, 1/3 of the cyclin c foci is still associated to the mitochondria in this mutant and they don't address it in the paper. How do you think is cyclin c being associated with the mitochondria then?

Question 1

  1. In the 2014 paper, they looked at a fis1 deletion mutant based on the idea that cyclin c is binding the the outer membrane of the mitochondria. However, 1/3 of the cyclin c foci is still associated to the mitochondria in this mutant and they don't address it in the paper. How do you think is cyclin c being associated with the mitochondria then?

Strich 2014

Question 2:

What other stress signals, along with extensive mitochondrial fission, could be contributing to the observed cell death?

Question 2:

What other stress signals, along with extensive mitochondrial fission, could be contributing to the observed cell death?

From the discussion (2014): 'However, extensive fission alone is not sufficient to induce cell death. Therefore, an additional stress signal appears required to evoke the final stages of the PCD pathway'.

Question 2:

What other stress signals, along with extensive mitochondrial fission, could be contributing to the observed cell death?

"Therefore, cyclin C appears to represent a different class of regulator that is necessary and sufficient for hyperfission but only necessary for efficient PCD"

 

2014 Strich Microb Cell

2015 Strich Genetics

Question 3

  1. These papers suggest that Cyclin C regulates both stress-induced gene expression in the nucleus (through interaction with Cdk8) and increased mitochondrial fission in the cytoplasm (by promoting Mdv1p-Dnm1p interaction). The protein CCNC is essential for development and loss of CCNC is embryonic lethal. Would it be possible to experimentally separate the nuclear and cytoplasmic functions of CCNC? Could you block translocation to the cytoplasm, and/or create a CCNC gene that doesn't ever localize to the nucleus?

Question 3

  1. experimentally separate nuclear/cytoplasmic functions of CCNC? Could you block translocation to the cytoplasm, and/or create a CCNC gene that doesn't ever localize to the nucleus?

Rostlab

Question 4

  1. Being that cyclin C plays an important role in the fragmentation of the mitochondrial network, how does it affect apoptosis in the context of tumor /cancer development?

Question 4

  1. Being that cyclin C plays an important role in the fragmentation of the mitochondrial network, how does it affect apoptosis in the context of tumor /cancer development?

"Heterozygous deletion of cyclin C gene (CCNC) has been linked to... ALL, osteosarcoma, and thyroid cancer, suggesting cyclin C is a bona fide tumor suppressor."

Strich 2018

Question 4

  1. Being that cyclin C plays an important role in the fragmentation of the mitochondrial network, how does it affect apoptosis in the context of tumor /cancer development?

Strich 2018

Question 5

  1. What are some possible mechanisms by which CDK8-CCNC could be driving meiotic gene expression in yeast?

Question 5

  1. What are some possible mechanisms by which CDK8-CCNC could be driving meiotic gene expression in yeast?

Inducer of meiosis 1 (IME1) regulates genes important for meiosis in yeast

 

IME1 induction delayed in CCNC-deficient (but slowly reaches maximal levels) or CDK8-deleted strains (maximal levels reduced)

 

"the molecular mechanism by which CDK8-CCNC drives meiotic gene expression program remains elusive"

 

 

Dannappel 2018

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