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CK2 as anti-stress factor

Masahiko Watabe1, Toshio Nakaki

  • 1Department of Pharmacology; Teikyo University School of Medicine; Tokyo, Japan.

Communicative & Integrative Biology
|August 17, 2012
PubMed

Insights

The protein kinase CK2 regulates aggresome formation by phosphorylating HDAC6, a key step in clearing misfolded protein aggregates. This mechanism is vital for cellular stress response and appears evolutionarily significant in higher primates.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Misfolded proteins can aggregate, disrupting cellular functions.
  • The ubiquitin-proteasome system degrades misfolded proteins; aggresomes form when this system is overwhelmed.
  • Aggresomes recruit misfolded proteins via HDAC6 and dynein motors for autophagic clearance.

Purpose of the Study:

  • To elucidate the mechanisms of aggresome assembly and clearance.
  • To investigate the role of protein kinase CK2 in aggresome formation.
  • To understand the regulation of HDAC6 activity in response to protein misfolding stress.

Main Methods:

  • Investigated the role of protein kinase CK2 in aggresome formation.
  • Analyzed the phosphorylation of HDAC6 at serine 458.
  • Examined the impact of HDAC6 phosphorylation on its deacetylase activity and aggresome dynamics.

Main Results:

  • Protein kinase CK2 phosphorylates HDAC6 on serine 458 under conditions of misfolded protein stress.
  • This phosphorylation enhances HDAC6 deacetylase activity.
  • Increased HDAC6 activity is critical for recruiting misfolded proteins to aggresomes and facilitating their clearance.
  • Serine 458 is conserved in humans and chimpanzees but not in other mammals, suggesting evolutionary significance.

Conclusions:

  • Protein kinase CK2 is a crucial regulator of aggresome assembly and clearance.
  • Phosphorylation of HDAC6 at serine 458 by CK2 is a key mechanism for managing misfolded protein aggregates.
  • This regulatory pathway highlights an evolutionarily conserved adaptation in higher primates for handling proteotoxic stress.
Keywords:
CK2aggresomedeacetylationdyneinhigher primatehistone deacetylase 6 (HDAC6)misfolded protein

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