LEK1 protein expression in normal and dysregulated cardiomyocyte mitosis.
A defining characteristic of embryonic cells is their ability to divide rapidly, even in tissues such as cardiac muscle, which cannot divide once fully differentiated. This suggests that regulators of cell division differ in embryonic and differentiated cells. LEK1 is a member of an emerging family of proteins with diverse functions but shared structural domains, including numerous leucine zippers, a nuclear localization site, and a functional Rb-binding domain. LEK1 is expressed ubiquitously in the developing mouse embryo from the earliest stages of differentiation through birth. It is absent in adult tissues, even those that maintain active cell division. We hypothesize that LEK1 is a regulator of mitosis restricted to the developing embryo and early neonate. Here, using BrdU incorporation, we show that LEK1 protein downregulation in cardiac myocytes correlates directly with cessation of DNA synthesis between neonatal days 6 and 10. In contrast, in an immortalized cardiac cell line (HL1 cells), both BrdU incorporation and LEK1 protein expression persist, and actively dividing cells express LEK1. However, BrdU incorporation can be decreased in these cells by treatment with a morpholino targeting LEK1 mRNA. These data suggest a role for LEK1 in regulating the normal embryonic cardiomyocyte cell cycle and in promoting continued mitosis in transformed, abnormally dividing cardiomyocytes.
Dees
Ellen
E
Gladys P. Stahlman Cardiovascular Research Laboratory, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
Robertson
J Brian
JB
Ashe
Mabelle
M
Pabón-Peña
Lil M
LM
Bader
David
D
Goodwin
Richard L
RL
D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation; D006321:Heart / Q000196:embryology / Q000502:physiology; D007150:Immunohistochemistry; D051379:Mice; D008813:Mice, Inbred ICR; D008840:Microfilament Proteins; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000502:physiology
D002868:Chromosomal Proteins, Non-Histone; D008840:Microfilament Proteins; C094772:centromere protein F