CAS/CSE protein family

Last updated
CAS/CSE protein, C-terminus
PDB 1z3h EBI.jpg
the exportin cse1 in its cargo-free, cytoplasmic state
Identifiers
SymbolCAS_CSE1
Pfam PF03378
InterPro IPR005043
Cse1
PDB 1z3h EBI.jpg
the exportin cse1 in its cargo-free, cytoplasmic state
Identifiers
SymbolCse1
Pfam PF08506
Pfam clan CL0020
InterPro IPR013713

In molecular biology, the CAS/CSE protein family is a family of proteins which includes mammalian cellular apoptosis susceptibility (CAS) proteins and yeast chromosome-segregation protein, CSE1. [1] CAS is involved in both cellular apoptosis and proliferation. [2] [3] Apoptosis is inhibited in CAS-depleted cells, while the expression of CAS correlates to the degree of cellular proliferation. Like CSE1, it is essential for the mitotic checkpoint in the cell cycle (CAS depletion blocks the cell in the G2 phase), and has been shown to be associated with the microtubule network and the mitotic spindle, [3] as is the protein MEK, which is thought to regulate the intracellular localization (predominantly nuclear vs. predominantly cytosolic) of CAS. In the nucleus, CAS acts as a nuclear transport factor in the importin pathway. [4] The importin pathway mediates the nuclear transport of several proteins that are necessary for mitosis and further progression. CAS is therefore thought to affect the cell cycle through its effect on the nuclear transport of these proteins. [5] Since apoptosis also requires the nuclear import of several proteins (such as P53 and transcription factors), it has been suggested that CAS also enables apoptosis by facilitating the nuclear import of at least a subset of these essential proteins. [6]

Members of the CAS/CSE family of proteins have two domains. An N-terminal Cse1 domain, which contains HEAT repeats, and a C-terminal domain. [7]

Related Research Articles

Cell nucleus Eukaryotic membrane-bounded organelle containing DNA

In cell biology, the nucleus is a membrane-bound organelle found in eukaryotic cells. Eukaryotes usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have no nuclei, and a few others including osteoclasts have many. The main structures making up the nucleus are the nuclear envelope, a double membrane that encloses the entire organelle and isolates its contents from the cellular cytoplasm; and the nuclear matrix, a network within the nucleus that adds mechanical support, much like the cytoskeleton supports the cell as a whole.

Cell cycle Series of events and stages that result in cell division

The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA and some of its organelles, and subsequently the partitioning of its cytoplasm and other components into two daughter cells in a process called cell division.

Nuclear pore

A nuclear pore is a part of a large complex of proteins, known as a nuclear pore complex that spans the nuclear envelope, which is the double membrane surrounding the eukaryotic cell nucleus. There are approximately 1,000 nuclear pore complexes (NPCs) in the nuclear envelope of a vertebrate cell, but it varies depending on cell type and the stage in the life cycle. The human nuclear pore complex (hNPC) is a 110 megadalton (MDa) structure. The proteins that make up the nuclear pore complex are known as nucleoporins; each NPC contains at least 456 individual protein molecules and is composed of 34 distinct nucleoporin proteins. About half of the nucleoporins typically contain solenoid protein domains—either an alpha solenoid or a beta-propeller fold, or in some cases both as separate structural domains. The other half show structural characteristics typical of "natively unfolded" or intrinsically disordered proteins, i.e. they are highly flexible proteins that lack ordered tertiary structure. These disordered proteins are the FG nucleoporins, so called because their amino-acid sequence contains many phenylalanine—glycine repeats.

Spindle apparatus Array of microtubules and associated molecules that forms between opposite poles of a eukaryotic cell during mitosis or meiosis and serves to move the duplicated chromosomes apart

In cell biology, the spindle apparatus refers to the cytoskeletal structure of eukaryotic cells that forms during cell division to separate sister chromatids between daughter cells. It is referred to as the mitotic spindle during mitosis, a process that produces genetically identical daughter cells, or the meiotic spindle during meiosis, a process that produces gametes with half the number of chromosomes of the parent cell.

Telophase Final stage of a cell division for eukaryotic cells both in mitosis and meiosis

Telophase is the final stage in both meiosis and mitosis in a eukaryotic cell. During telophase, the effects of prophase and prometaphase are reversed. As chromosomes reach the cell poles, a nuclear envelope is re-assembled around each set of chromatids, the nucleoli reappear, and chromosomes begin to decondense back into the expanded chromatin that is present during interphase. The mitotic spindle is disassembled and remaining spindle microtubules are depolymerized. Telophase accounts for approximately 2% of the cell cycle's duration.

Importin is a type of karyopherin that transports protein molecules from the cell's cytoplasm to the nucleus. It does so by binding to specific recognition sequences, called nuclear localization sequences (NLS).

Ran (protein) GTPase functioning in nuclear transport

Ran also known as GTP-binding nuclear protein Ran is a protein that in humans is encoded by the RAN gene. Ran is a small 25 kDa protein that is involved in transport into and out of the cell nucleus during interphase and also involved in mitosis. It is a member of the Ras superfamily.

Karyopherin alpha 2

Importin subunit alpha-2 is a protein that in humans is encoded by the KPNA2 gene.

KPNB1 Protein-coding gene in the species Homo sapiens

Importin subunit beta-1 is a protein that in humans is encoded by the KPNB1 gene.

IPO5

Importin-5 is a protein that in humans is encoded by the IPO5 gene. The protein encoded by this gene is a member of the importin beta family. Structurally, the protein adopts the shape of a right hand solenoid and is composed of 24 HEAT repeats.

BCL2-related protein A1

Bcl-2-related protein A1 is a protein that in humans is encoded by the BCL2A1 gene.

PTPN2

Tyrosine-protein phosphatase non-receptor type 2 is an enzyme that in humans is encoded by the PTPN2 gene.

Nucleoporin 214

Nucleoporin 214 (Nup2014) is a protein that in humans is encoded by the NUP214 gene.

HMGN1

Non-histone chromosomal protein HMG-14 is a protein that in humans is encoded by the HMGN1 gene.

BUB3

Mitotic checkpoint protein BUB3 is a protein that in humans is encoded by the BUB3 gene.

DDX11

Probable ATP-dependent RNA helicase DDX11 is an enzyme that in humans is encoded by the DDX11 gene.

UBE4B

Ubiquitin conjugation factor E4 B is a protein that in humans is encoded by the UBE4B gene.

Wee1

Wee1 is a nuclear kinase belonging to the Ser/Thr family of protein kinases in the fission yeast Schizosaccharomyces pombe. Wee1 has a molecular mass of 96 kDa and is a key regulator of cell cycle progression. It influences cell size by inhibiting the entry into mitosis, through inhibiting Cdk1. Wee1 has homologues in many other organisms, including mammals.

Importin alpha, or karyopherin alpha refers to a class of adaptor proteins that are involved in the import of proteins into the cell nucleus. They are a sub-family of karyopherin proteins.

IPO8

Importin 8 is a protein that in humans is encoded by the IPO8 gene.

References

  1. ↑ Brinkmann U, Brinkmann E, Gallo M, Pastan I (October 1995). "Cloning and characterization of a cellular apoptosis susceptibility gene, the human homologue to the yeast chromosome segregation gene CSE1". Proc. Natl. Acad. Sci. U.S.A. 92 (22): 10427–31. Bibcode:1995PNAS...9210427B. doi: 10.1073/pnas.92.22.10427 . PMC   40810 . PMID   7479798.
  2. ↑ Brinkmann U, Brinkmann E, Gallo M, Scherf U, Pastan I (May 1996). "Role of CAS, a human homologue to the yeast chromosome segregation gene CSE1, in toxin and tumor necrosis factor mediated apoptosis". Biochemistry. 35 (21): 6891–9. doi:10.1021/bi952829+. PMID   8639641.
  3. 1 2 Scherf U, Pastan I, Willingham MC, Brinkmann U (April 1996). "The human CAS protein which is homologous to the CSE1 yeast chromosome segregation gene product is associated with microtubules and mitotic spindle". Proc. Natl. Acad. Sci. U.S.A. 93 (7): 2670–4. Bibcode:1996PNAS...93.2670S. doi: 10.1073/pnas.93.7.2670 . PMC   39688 . PMID   8610099.
  4. ↑ Kutay U, Bischoff FR, Kostka S, Kraft R, Gorlich D (September 1997). "Export of importin alpha from the nucleus is mediated by a specific nuclear transport factor". Cell. 90 (6): 1061–71. doi: 10.1016/S0092-8674(00)80372-4 . PMID   9323134. S2CID   16092404.
  5. ↑ Kutay U, Bischoff FR, Kostka S, Kraft R, Görlich D (September 1997). "Export of importin alpha from the nucleus is mediated by a specific nuclear transport factor". Cell. 90 (6): 1061–71. doi: 10.1016/S0092-8674(00)80372-4 . PMID   9323134. S2CID   16092404.
  6. ↑ Brinkmann U (March 1998). "CAS, the human homologue of the yeast chromosome-segregation gene CSE1, in proliferation, apoptosis, and cancer". Am. J. Hum. Genet. 62 (3): 509–13. doi:10.1086/301773. PMC   1376967 . PMID   9497270.
  7. ↑ Cook, A.; Fernandez, E.; Lindner, D.; Ebert, J.; Schlenstedt, G.; Conti, E. (2005). "The Structure of the Nuclear Export Receptor Cse1 in Its Cytosolic State Reveals a Closed Conformation Incompatible with Cargo Binding". Molecular Cell. 18 (3): 355–367. doi: 10.1016/j.molcel.2005.03.021 . PMID   15866177.
This article incorporates text from the public domain Pfam and InterPro: IPR005043
This article incorporates text from the public domain Pfam and InterPro: IPR013713
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