Кузина Екатерина Сергеевна


Эл. почта: kat.kuzina@gmail.com

Избранные публикации

  1. Belogurov A., Kudriaeva A., Kuzina E., Smirnov I., Bobik T., Ponomarenko N., KravtsovaIvantsiv Y., Ciechanover A., Gabibov A. (2014). Multiple Sclerosis Autoantigen Myelin Basic Protein Escapes Control by Ubiquitination During Proteasomal Degradation. J. Biol. Chem. , [+]

    The vast majority of cellular proteins are degraded by the 26S proteasome after their ubiquitination. Here, we report that the major component of the myelin multilayered membrane sheath, myelin basic protein (MBP), is hydrolyzed by the 26S proteasome in a ubiquitin-independent manner both in vitro and in mammalian cells. As a proteasomal substrate, MBP reveals a distinct and physiologically relevant concentration range for ubiquitin-independent proteolysis. Enzymatic deimination prevents hydrolysis of MBP by the proteasome, suggesting that an abnormally basic charge contributes to its susceptibility towards proteasome-mediated degradation. To our knowledge, our data reveal the first case of a pathophysiologically important autoantigen as a ubiquitin-independent substrate of the 26S proteasome.

    ID:1013
  2. Kuzina E., Kudriaeva A., Smirnov I., Dubina M.V., Gabibov A., Belogurov A. (2014). Glatiramer Acetate and Nanny Proteins Restrict Access of the Multiple Sclerosis Autoantigen Myelin Basic Protein to the 26S Proteasome. Biomed Res Int 2014, 926394 [+]

    We recently showed that myelin basic protein (MBP) is hydrolyzed by 26S proteasome without ubiquitination. The previously suggested concept of charge-mediated interaction between MBP and the proteasome led us to attempt to compensate or mimic its positive charge to inhibit proteasomal degradation. We demonstrated that negatively charged actin and calmodulin (CaM), as well as basic histone H1.3, inhibit MBP hydrolysis by competing with the proteasome and MBP, respectively, for binding their counterpart. Interestingly, glatiramer acetate (GA), which is used to treat multiple sclerosis (MS) and is structurally similar to MBP, inhibits intracellular and in vitro proteasome-mediated MBP degradation. Therefore, the data reported in this study may be important for myelin biogenesis in both the normal state and pathophysiological conditions.

    ID:1089